Skip to main content

RNA–Protein Interactions: An Overview

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1097))

Abstract

RNA binding proteins (RBPs) are key players in the regulation of gene expression. In this chapter we discuss the main protein–RNA recognition modes used by RBPs in order to regulate multiple steps of RNA processing. We discuss traditional and state-of-the-art technologies that can be used to study RNAs bound by individual RBPs, or vice versa, for both in vitro and in vivo methodologies. To help highlight the biological significance of RBP mediated regulation, online resources on experimentally verified protein–RNA interactions are briefly presented. Finally, we present the major tools to computationally infer RNA binding sites according to the modeling features and to the unsupervised or supervised frameworks that are adopted. Since some RNA binding site search algorithms are derived from DNA binding site search algorithms, we discuss the commonalities and novelties introduced to handle both sequence and structural features uniquely characterizing protein–RNA interactions.

This is a preview of subscription content, log in via an institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Dieci G, Ruotolo R, Braglia P, Carles C, Carpentieri A, Amoresano A, Ottonello S (2009) Positive modulation of RNA polymerase III transcription by ribosomal proteins. Biochem Biophys Res Commun 379(2):489–493. doi:10.1016/j.bbrc.2008. 12.097

    Article  CAS  PubMed  Google Scholar 

  2. Wan F, Anderson DE, Barnitz RA, Snow A, Bidere N, Zheng L, Hegde V, Lam LT, Staudt LM, Levens D, Deutsch WA, Lenardo MJ (2007) Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation. Cell 131(5):927–939. doi:10.1016/j.cell.2007.10.009

    Article  CAS  PubMed  Google Scholar 

  3. Whitelaw E, Proudfoot N (1986) Alpha-thalassaemia caused by a poly(a) site mutation reveals that transcriptional termination is linked to 3’ end processing in the human alpha 2 globin gene. EMBO J 5(11):2915–2922. http://www.hubmed.org/fulltext.cgi?uids=3024968

    Google Scholar 

  4. Lareau LF, Inada M, Green RE, Wengrod JC, Brenner SE (2007) Unproductive splicing of sr genes associated with highly conserved and ultraconserved dna elements. Nature 446(7138):926–929. doi:10.1038/nature05676

    Article  CAS  PubMed  Google Scholar 

  5. Holt CE, Bullock SL (2009) Subcellular mRNA localization in animal cells and why it matters. Science 326(5957):1212–1216. doi:10.1126/science.1176488

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Bertrand E, Chartrand P, Schaefer M, Shenoy SM, Singer RH, Long RM (1998) Localization of ASH1 mRNA particles in living yeast. Mol Cell 2(4):437–445. http://www.hubmed.org/fulltext.cgi?uids=9809065

    Google Scholar 

  7. Lécuyer E, Yoshida H, Parthasarathy N, Alm C, Babak T, Cerovina T, Hughes TR, Tomancak P, Krause HM (2007) Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function. Cell 131(1):174–187. doi:10.1016/j.cell. 2007.08.003. http://www.hubmed.org/fulltext.cgi? uids=17923096

    Google Scholar 

  8. Grünwald D, Singer RH, Rout M (2011) Nuclear export dynamics of RNA-protein complexes. Nature 475(7356):333–341 doi:10.1038/nature10318

    Article  PubMed Central  PubMed  Google Scholar 

  9. Wolke U, Weidinger G, Köprunner M, Raz E (2002) Multiple levels of posttranscriptional control lead to germ line-specific gene expression in the zebrafish. Curr Biol 12(4):289–294

    Article  CAS  PubMed  Google Scholar 

  10. Lipshitz HD, Smibert CA (2000) Mechanisms of RNA localization and translational regulation. Curr Opin Genet Dev 10(5):476–488. http://www.hubmed.org/fulltext.cgi?uids=10980424

    Google Scholar 

  11. Chartrand P, Meng XH, Huttelmaier S, Donato D, Singer RH (2002) Asymmetric sorting of ash1p in yeast results from inhibition of translation by localization elements in the mRNA. Mol Cell 10(6):1319–1330

    Article  CAS  PubMed  Google Scholar 

  12. Lewis RA, Kress TL, Cote CA, Gautreau D, Rokop ME, Mowry KL (2004) Conserved and clustered RNA recognition sequences are a critical feature of signals directing RNA localization in xenopus oocytes. Mech Dev 121(1):101–109

    Article  CAS  PubMed  Google Scholar 

  13. Macdonald PM, Struhl G (1988) cis-acting sequences responsible for anterior localization of bicoid mRNA in drosophila embryos. Nature 336(6199):595–598. doi:10.1038/ 336595a0

    Article  CAS  PubMed  Google Scholar 

  14. Cenik C, Chua HN, Zhang H, Tarnawsky SP, Akef A, Derti A, Tasan M, Moore MJ, Palazzo AF, Roth FP (2011) Genome analysis reveals interplay between 5’utr introns and nuclear mRNA export for secretory and mitochondrial genes. PLoS Genet 7(4). doi:10.1371/journal.pgen.1001366. http://www.hubmed.org/fulltext.cgi?uids=21533221

    Google Scholar 

  15. Palazzo AF, Springer M, Shibata Y, Lee CS, Dias AP, Rapoport TA (2007) The signal sequence coding region promotes nuclear export of mRNA. PLoS Biol 5(12). doi:10.1371/journal.pbio.0050322. http://www.hubmed.org/fulltext.cgi?uids=18052610

    Google Scholar 

  16. Arn EA, Cha BJ, Theurkauf WE, Macdonald PM (2003) Recognition of a bicoid mRNA localization signal by a protein complex containing swallow, nod, and RNA binding proteins. Dev Cell 4(1):41–51

    Article  CAS  PubMed  Google Scholar 

  17. Müller M, Heym RG, Mayer A, Kramer K, Schmid M, Cramer P, Urlaub H, Jansen RP, Niessing D (2011) A cytoplasmic complex mediates specific mRNA recognition and localization in yeast. PLoS Biol 9(4). doi:10.1371/journal.pbio.1000611. http://www.hubmed.org/fulltext.cgi?uids=21526221

    Google Scholar 

  18. Tadros W, Goldman AL, Babak T, Menzies F, Vardy L, Orr-Weaver T, Hughes TR, Westwood JT, Smibert CA, Lipshitz HD (2007) Smaug is a major regulator of maternal mRNA destabilization in drosophila and its translation is activated by the PAN GU kinase. Dev Cell 12(1):143–55. doi:10.1016/j.devcel.2006.10.005

    Article  CAS  PubMed  Google Scholar 

  19. Forrest KM, Gavis ER (2003) Live imaging of endogenous RNA reveals a diffusion and entrapment mechanism for nanos mRNA localization in drosophila. Curr Biol 13(14):1159–1168

    Article  CAS  PubMed  Google Scholar 

  20. Gebauer F, Hentze MW (2004) Molecular mechanisms of translational control. Nat Rev Mol Cell Biol 5(10):827–835. doi:10.1038/nrm1488

    Article  CAS  PubMed  Google Scholar 

  21. Jackson RJ, Hellen CUT, Pestova TV (2010) The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Mol Cell Biol 11(2):113–127. doi:10.1038/nrm2838

    Article  CAS  PubMed  Google Scholar 

  22. Loh PG, Song H (2010) Structural and mechanistic insights into translation termination. Curr Opin Struct Biol 20(1):98–103. doi:10.1016/j.sbi.2009.12.005

    Article  CAS  PubMed  Google Scholar 

  23. Gingold H, Pilpel Y (2011) Determinants of translation efficiency and accuracy. Mol Syst Biol 7:481. doi:10.1038/msb.2011.14

    Article  PubMed Central  PubMed  Google Scholar 

  24. Dever TE (2002) Gene-specific regulation by general translation factors. Cell 108(4):545–556

    Article  CAS  PubMed  Google Scholar 

  25. Muckenthaler M, Gray NK, Hentze MW (1998) Irp-1 binding to ferritin mRNA prevents the recruitment of the small ribosomal subunit by the cap-binding complex eif4f. Mol Cell 2(3):383–388

    Article  CAS  PubMed  Google Scholar 

  26. Gebauer F, Grskovic M, Hentze MW (2003) Drosophila sex-lethal inhibits the stable association of the 40S ribosomal subunit with msl-2 mRNA. Mol Cell 11(5):1397–1404

    Article  CAS  PubMed  Google Scholar 

  27. Grskovic M, Hentze MW, Gebauer F (2003) A co-repressor assembly nucleated by sex-lethal in the 3’utr mediates translational control of drosophila msl-2 mRNA. EMBO J 22(20):5571–5581. doi:10.1093/emboj/cdg539

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Beckmann K, Grskovic M, Gebauer F, Hentze MW (2005) A dual inhibitory mechanism restricts msl-2 mRNA translation for dosage compensation in drosophila. Cell 122(4):529–540. doi:10.1016/j.cell.2005. 06.011

    Article  CAS  PubMed  Google Scholar 

  29. Nelson MR, Leidal AM, Smibert CA (2004) Drosophila cup is an eif4e-binding protein that functions in smaug-mediated translational repression. EMBO J 23(1):150–159. doi:10.1038/sj.emboj.7600026

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Nakamura A, Sato K, Hanyu-Nakamura K (2004) Drosophila cup is an eif4e binding protein that associates with bruno and regulates oskar mRNA translation in oogenesis. Dev Cell 6(1):69–78

    Article  CAS  PubMed  Google Scholar 

  31. Stebbins-Boaz B, Cao Q, de Moor CH, Mendez R, Richter JD (1999) Maskin is a cpeb-associated factor that transiently interacts with elf-4e. Mol Cell 4(6):1017–1027

    Article  CAS  PubMed  Google Scholar 

  32. Ostareck DH, Ostareck-Lederer A, Shatsky IN, Hentze MW (2001) Lipoxygenase mRNA silencing in erythroid differentiation: The 3’utr regulatory complex controls 60S ribosomal subunit joining. Cell 104(2):281–290

    Article  CAS  PubMed  Google Scholar 

  33. Chaudhury A, Hussey GS, Ray PS, Jin G, Fox PL, Howe PH (2010) TGF-beta-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI. Nat Cell Biol 12(3):286–293. doi:10.1038/ncb2029

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Hussey GS, Chaudhury A, Dawson AE, Lindner DJ, Knudsen CR, Wilce MCJ, Merrick WC, Howe PH (2011) Identification of an mRNP complex regulating tumorigenesis at the translational elongation step. Mol Cell 41(4): 419–431. doi:10.1016/j.molcel. 2011.02.003

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Doma MK, Parker R (2007) RNA quality control in eukaryotes. Cell 131(4):660–668. doi:10.1016/j.cell.2007.10.041

    Article  CAS  PubMed  Google Scholar 

  36. Villalba A, Coll O, Gebauer F (2011) Cytoplasmic polyadenylation and translational control. Curr Opin Genet Dev 21(4):452–457. doi:10.1016/j.gde.2011. 04.006

    Article  CAS  PubMed  Google Scholar 

  37. Piqué M, López JM, Foissac S, Guigó R, Méndez R (2008) A combinatorial code for cpe-mediated translational control. Cell 132(3):434–448. doi:10.1016/j.cell. 2007.12.038

    Article  PubMed  Google Scholar 

  38. Kim KW, Nykamp K, Suh N, Bachorik JL, Wang L, Kimble J (2009) Antagonism between gld-2 binding partners controls gamete sex. Dev Cell 16(5):723–733. doi:10.1016/j.devcel.2009.04.002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Reed R, Hurt E (2002) A conserved mRNA export machinery coupled to pre-mRNA splicing. Cell 108(4):523–531

    Article  CAS  PubMed  Google Scholar 

  40. Houseley J, LaCava J, Tollervey D (2006) RNA-quality control by the exosome. Nat Rev Mol Cell Biol 7(7):529–539 doi:10.1038/nrm1964.

    Article  CAS  PubMed  Google Scholar 

  41. LaCava J, Houseley J, Saveanu C, Petfalski E, Thompson E, Jacquier A, Tollervey D (2005) RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121(5):713–724. doi:10.1016/j.cell.2005.04.029

    Article  CAS  PubMed  Google Scholar 

  42. Isken O, Maquat LE (2008) The multiple lives of nmd factors: balancing roles in gene and genome regulation. Nat Rev Genet 9(9):699–712. doi:10.1038/nrg2402

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Kong J, Liebhaber SA (2007) A cell type-restricted mRNA surveillance pathway triggered by ribosome extension into the 3’ untranslated region. Nat Struct Mol Biol 14(7):670–676. doi:10.1038/nsmb1256

    Article  CAS  PubMed  Google Scholar 

  44. Hir HL, Gatfield D, Izaurralde E, Moore MJ (2001) The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J 20(17):4987–4997. doi:10.1093/emboj/20.17.4987

    Article  PubMed Central  PubMed  Google Scholar 

  45. Behm-Ansmant I, Gatfield D, Rehwinkel J, Hilgers V, Izaurralde E (2007) A conserved role for cytoplasmic poly(a)-binding protein 1 (pabpc1) in nonsense-mediated mRNA decay. EMBO J 26(6):1591–601. doi:10.1038/sj.emboj.7601588

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. González CI, Ruiz-Echevarría MJ, Vasudevan S, Henry MF, Peltz SW (2000) The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated mRNA decay. Mol Cell 5(3):489–499

    Article  PubMed  Google Scholar 

  47. Hwang J, Sato H, Tang Y, Matsuda D, Maquat LE (2010) Upf1 association with the cap-binding protein, cbp80, promotes nonsense-mediated mRNA decay at two distinct steps. Mol Cell 39(3):396–409. doi:10.1016/j.molcel.2010.07.004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Ruiz-Echevarría MJ, Peltz SW (2000) The RNA binding protein pub1 modulates the stability of transcripts containing upstream open reading frames. Cell 101(7):741–751

    Article  PubMed  Google Scholar 

  49. Chester A, Somasekaram A, Tzimina M, Jarmuz A, Gisbourne J, O’Keefe R, Scott J, Navaratnam N (2003) The apolipoprotein b mRNA editing complex performs a multifunctional cycle and suppresses nonsense-mediated decay. EMBO J 22(15)3971–3982. doi:10.1093/emboj/cdg369

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Stalder L, Mühlemann O (2008) The meaning of nonsense. Trends Cell Biol 18(7):315–321. doi:10.1016/j.tcb.2008.04.005

    Article  CAS  PubMed  Google Scholar 

  51. Inada T, Aiba H (2005) Translation of aberrant mRNAs lacking a termination codon or with a shortened 3’-UTR is repressed after initiation in yeast. EMBO J 24(8):1584–1595. doi:10.1038/sj.emboj.7600636

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Kim YK, Furic L, Desgroseillers L, Maquat LE (2005) Mammalian Staufen1 recruits Upf1 to specific mRNA 3’UTRs so as to elicit mRNA decay. Cell 120(2):195–208. doi:10.1016/j.cell.2004.11.050

    Article  CAS  PubMed  Google Scholar 

  53. Kaygun H, Marzluff WF (2005) Translation termination is involved in histone mRNA degradation when DNA replication is inhibited. Mol Cell Biol 25(16):6879–6888. doi:10.1128/MCB.25.16.6879-6888.2005

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Wulff BE, Sakurai M, Nishikura K (2011) Elucidating the inosinome: global approaches to adenosine-to-inosine RNA editing. Nat Rev Genet 12(2):81–85. doi:10.1038/nrg2915. http://www.hubmed.org/fulltext.cgi?uids=21173775

    Google Scholar 

  55. Bass BL (2002) RNA editing by adenosine deaminases that act on RNA. Annu Rev Biochem 71:817–846. doi:10.1146/annurev.biochem.71.110601. 135501. http://www.hubmed.org/fulltext.cgi?uids=12045112

    Google Scholar 

  56. Eggington JM, Greene T, Bass BL (2011) Predicting sites of adar editing in double-stranded RNA. Nat Commun 2:319–319. doi:10.1038/ncomms1324. http://www.hubmed.org/fulltext.cgi?uids=21587236

    Google Scholar 

  57. Hundley HA, Bass BL (2010) Adar editing in double-stranded utrs and other noncoding RNA sequences. Trends Biochem Sci 35(7):377–383. doi:10.1016/j.tibs.2010. 02.008. http://www.hubmed.org/fulltext.cgi?uids=20382028

    Google Scholar 

  58. Jepson JE, Reenan RA (2008) RNA editing in regulating gene expression in the brain. Biochim Biophys Acta 1779(8):59–470. doi:10. 1016/j.bbagrm.2007.11.009. http://www.hubmed.org/fulltext.cgi?uids=18086576

    Google Scholar 

  59. Hoopengardner B, Bhalla T, Staber C, Reenan R (2003) Nervous system targets of RNA editing identified by comparative genomics. Science 301(5634):832–836. doi: 10.1126/science.1086763. http://www.hubmed.org/fulltext.cgi? uids=12907802

    Google Scholar 

  60. Paz-Yaacov N, Levanon EY, Nevo E, Kinar Y, Harmelin A, Jacob-Hirsch J, Amariglio N, Eisenberg E, Rechavi G (2010) Adenosine-to-inosine RNA editing shapes transcriptome diversity in primates. Proc Natl Acad Sci USA 107(27):12174–12179. doi:10.1073/pnas.1006183107. http://www.hubmed.org/fulltext.cgi?uids=20566853

    Google Scholar 

  61. Nishikura K (2010) Functions and regulation of RNA editing by adar deaminases. Annu Rev Biochem 79:321–349. doi:10.1146/annurev-biochem-060208-105251. http://www.hubmed.org/fulltext.cgi?uids=20192758

  62. Chen SH, Habib G, Yang CY, Gu ZW, Lee BR, Weng SA, Silberman SR, Cai SJ, Deslypere JP, Rosseneu M (1987) Apolipoprotein b-48 is the product of a messenger RNA with an organ-specific in-frame stop codon. Science 238(4825):363–366. http://www.hubmed.org/fulltext.cgi?uids=3659919

    Google Scholar 

  63. Powell LM, Wallis SC, Pease RJ, Edwards YH, Knott TJ, Scott J (1987) A novel form of tissue-specific RNA processing produces apolipoprotein-b48 in intestine. Cell 50(6):831–840. http://www.hubmed.org/fulltext.cgi?uids=3621347

    Google Scholar 

  64. Rosenberg BR, Hamilton CE, Mwangi MM, Dewell S, Papavasiliou FN (2011) Transcriptome-wide sequencing reveals numerous apobec1 mrna-editing targets in transcript 3’ UTRs. Nat Struct Mol Biol 18(2):230–236. doi:10.1038/nsmb.1975. http://www.hubmed.org/fulltext.cgi?uids=21258325

  65. Li M, Wang IX, Li Y, Bruzel A, Richards AL, Toung JM, Cheung VG (2011) Widespread RNA and DNA sequence differences in the human transcriptome. Science 333 (6038):53–58. doi:10.1126/science.12 07018. http://www.hubmed.org/fulltext.cgi?uids=21258325

    Google Scholar 

  66. Schrider DR, Gout JF, Hahn MW (2011) Very few RNA and DNA sequence differences in the human transcriptome. PLoS One 6(10). doi:10.1371/journal.pone.0025842. http://www.hubmed.org/fulltext.cgi?uids=22022455

  67. Barreau C, Paillard L, Osborne HB (2005) Au-rich elements and associated factors: are there unifying principles? Nucleic Acids Res 33(22):7138–7150. doi:10.1093/nar/gki1012

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Lal A, Mazan-Mamczarz K, Kawai T, Yang X, Martindale JL, Gorospe M (2004) Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs. EMBO J 23(15):3092–3102. doi:10.1038/sj.emboj.7600305

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Sobue S, Murakami M, Banno Y, Ito H, Kimura A, Gao S, Furuhata A, Takagi A, Kojima T, Suzuki M, Nozawa Y, Murate T (2008) v-Src oncogene product increases sphingosine kinase 1 expression through mRNA stabilization: alteration of AU-rich element-binding proteins. Oncogene 27(46):6023–6033. doi:10.1038/onc. 2008.198

    Article  CAS  PubMed  Google Scholar 

  70. Kedde M, Strasser MJ, Boldajipour B, Oude Vrielink JA, Slanchev K, le Sage C, Nagel R, Voorhoeve PM, van Duijse J, Ørom UA, Lund AH, Perrakis A, Raz E, Agami R (2007) RNA-binding protein Dnd1 inhibits microRNA access to target mRNA. Cell 131(7):1273–1286. doi:10.1016/j.cell.2007.11.034

    Article  CAS  PubMed  Google Scholar 

  71. Burns DM, D’Ambrogio A, Nottrott S, Richter JD (2011) Cpeb and two poly(a) polymerases control mir-122 stability and p53 mRNA translation. Nature 473(7345):105–108. doi:10.1038/nature09908

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Abdelmohsen K, Hutchison ER, Lee EK, Kuwano Y, Kim MM, Masuda K, Srikantan S, Subaran SS, Marasa BS, Mattson MP, Gorospe M (2010) miR-375 inhibits differentiation of neurites by lowering HuD levels. Mol Cell Biol 30(17):4197–4210. doi:10.1128/MCB.00316-10

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Deschenes-Furry J, Perrone-Bizzozero N, Jasmin BJ (2006) The RNA-binding protein HuD: a regulator of neuronal differentiation, maintenance and plasticity. Bioessays 28:822–833

    Article  CAS  PubMed  Google Scholar 

  74. Lukong K, Chang K, Khandjian E, Richard S (2008) RNA-binding proteins in human genetic disease. Trends Genet 24(8):416–425. ISSN 01689525. doi:10.1016/j.tig. 2008.05.004. http://linkinghub.elsevier.com/retrieve/pii/S016895250800173X

    Google Scholar 

  75. Yang YY, Yin GL, Darnell RB (1998) The neuronal RNA-binding protein Nova-2 is implicated as the autoantigen targeted in POMA patients with dementia. Proc Natl Acad Sci USA 95:13254–13259

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Song L, Wang L, Li Y, Xiong H, Wu J, Li J, Li M (2010) Sam68 up-regulation correlates with, and its down-regulation inhibits, proliferation and tumourigenicity of breast cancer cells. J Pathol 222:227–237

    Article  CAS  PubMed  Google Scholar 

  77. Busa R, Paronetto MP, Farini D, Pierantozzi E, Botti F, Angelini DF, Attisani F, Vespasiani G, Sette C (2007) The RNA-binding protein sam68 contributes to proliferation and survival of human prostate cancer cells. Oncogene 26(30):4372–4382. ISSN 0950-9232. http://dx.doi.org/10.1038/sj.onc.1210224

    Google Scholar 

  78. Wang R, Geng J, Wang JH, Chu XY, Geng HC, Chen LB (2009) Overexpression of eukaryotic initiation factor 4E (eIF4E) and its clinical significance in lung adenocarcinoma. Lung Cancer 66:237–244

    Article  PubMed  Google Scholar 

  79. Keene JD (2007) RNA regulons: coordination of post-transcriptional events. Nat Rev Genet 8(7):533–543. ISSN 1471-0056. doi:10.1038/nrg2111. http://www.nature.com/doifinder/10.1038/nrg2111

    Google Scholar 

  80. Cléry A, Blatter M, Allain FH (2008) RNA recognition motifs: boring? not quite. Curr Opin Struct Biol 18(3):290–298. doi:10.1016/j.sbi.2008.04.002. http://www.hubmed.org/fulltext.cgi?uids=18515081

  81. Oberstrass FC, Auweter SD, Erat M, Hargous Y, Henning A, Wenter P, Reymond L, Amir-Ahmady B, Pitsch S, Black DL, Allain FH (2005) Structure of PTB bound to RNA: specific binding and implications for splicing regulation. Science 309(5743):2054–2057. doi:10.1126/science.1114066. http://www.hubmed.org/fulltext.cgi?uids=16179478

    Google Scholar 

  82. Lewis HA, Musunuru K, Jensen KB, Edo C, Chen H, Darnell RB, Burley SK (2000) Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome. Cell 100(3):323–332

    Article  CAS  PubMed  Google Scholar 

  83. Liu Z, Luyten I, Bottomley MJ, Messias AC, Houngninou-Molango S, Sprangers R, Zanier K, Krämer A, Sattler M (2001) Structural basis for recognition of the intron branch site RNA by splicing factor 1. Science 294(5544):1098–1102. doi:10.1126/science.1064719

    Article  CAS  PubMed  Google Scholar 

  84. Beuth B, Pennell S, Arnvig KB, Martin SR, Taylor IA (2005) Structure of a mycobacterium tuberculosis nusa-rna complex. EMBO J 24(20):3576–3587. doi:10.1038/sj.emboj.7600829

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Diges CM, Uhlenbeck OC (2001) Escherichia coli DbpA is an RNA helicase that requires hairpin 92 of 23S RNA. EMBO J 20(19):5503–5512. doi:10.1093/emboj/20.19.5503

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Wang S, Hu Y, Overgaard MT, Karginov FV, Uhlenbeck OC, McKay DB (2006) The domain of the Bacillus subtilis DEAD-box helicase YxiN that is responsible for specific binding of 23S rRNA has an RNA recognition motif fold. RNA 12(6):959–967. doi:10.1261/rna.5906

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Wang Y, Juranek S, Li H, Sheng G, Wardle GS, Tuschl T, Patel DJ (2009) Nucleation, propagation and cleavage of target rnas in ago silencing complexes. Nature 461(7265):754–761. doi:10.1038/nature08434

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Siomi MC, Sato K, Pezic D, Aravin AA (2011) Piwi-interacting small RNAs: the vanguard of genome defence. Nat Rev Mol Cell Biol 12(4):246–258. doi:10.1038/ nrm3089

    Article  CAS  PubMed  Google Scholar 

  89. Wilusz CJ, Wilusz J (2005) Eukaryotic Lsm proteins: lessons from bacteria. Nat Struct Mol Biol 12(12):1031–1036. doi:10. 1038/nsmb1037. http://www.hubmed.org/fulltext.cgi?uids=16327775

    Google Scholar 

  90. Qiao F, Bowie JU (2005) The many faces of SAM. Sci STKE 2005(286). doi:10.1126/ stke.2862005re7. http://www.hubmed.org/fulltext.cgi?uids=15928333

  91. Aviv T, Lin Z, Ben-Ari G, Smibert CA, Sicheri F (2006) Sequence-specific recognition of RNA hairpins by the SAM domain of Vts1p. Nat Struct Mol Biol 13(2):168–176. doi:10.1038/nsmb1053. http://www.hubmed.org/fulltext.cgi?uids=16429151

  92. Oberstrass FC, Lee A, Stefl R, Janis M, Chanfreau G, Allain FH (2006) Shape-specific recognition in the structure of the Vts1p SAM domain with RNA. Nat Struct Mol Biol 13(2):160–167. doi:10.1038/nsmb1038. http://www.hubmed.org/fulltext.cgi?uids=16429156

  93. Stefl R, Skrisovska L, Allain FH-T (2005) RNA sequence- and shape-dependent recognition by proteins in the ribonucleoprotein particle. EMBO Rep 6(1):33–38. doi:10.1038/sj.embor.7400325

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Lunde BM, Moore C, Varani G (2007) RNA-binding proteins: modular design for efficient function. Nat Rev Mol Cell Biol 8(6):479–490. doi:10.1038/nrm2178

    Article  CAS  PubMed  Google Scholar 

  95. Mazza C, Segref A, Mattaj IW, Cusack S (2002) Large-scale induced fit recognition of an m(7)GpppG cap analogue by the human nuclear cap-binding complex. EMBO J 21(20):5548–5557

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Mackay JP, Font J, Segal DJ (2011) The prospects for designer single-stranded rna-binding proteins. Nat Struct Mol Biol 18(3):256–261. doi:10.1038/nsmb.2005

    Article  CAS  PubMed  Google Scholar 

  97. Gagnon KT, Maxwell ES (2011) Electrophoretic mobility shift assay for characterizing rna-protein interaction. Method Mol Biol 703:275–291. doi:10.1007/978-1-59745-248-9-19

    Article  CAS  Google Scholar 

  98. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage t4 DNA polymerase. Science 249(4968):505–510. http://www.hubmed.org/fulltext.cgi?uids=2200121

    Google Scholar 

  99. Ray D, Kazan H, Chan ET, Peña Castillo L, Chaudhry S, Talukder S, Blencowe BJ, Morris Q, Hughes TR (2009) Rapid and systematic analysis of the rna recognition specificities of RNA-binding proteins. Nat Biotechnol 27(7):667–670. doi:10.1038/nbt.1550

    Article  CAS  PubMed  Google Scholar 

  100. Keene JD, Komisarow JM, Friedersdorf MB (2006) Rip-chip: the isolation and identification of mRNAs, microRNAs and protein components of ribonucleoprotein complexes from cell extracts. Nat Protoc 1(1):302–307. doi:10.1038/nprot.2006.47

    Article  CAS  PubMed  Google Scholar 

  101. Mili S, Steitz JA (2004) Evidence for reassociation of rna-binding proteins after cell lysis: implications for the interpretation of immunoprecipitation analyses. RNA 10(11):1692–1694. doi:10.1261/rna.7151404

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  102. Zhang C, Darnell RB (2011) Mapping in vivo protein-RNA interactions at single-nucleotide resolution from hits-clip data. Nat Biotechnol 29(7):607–614. doi:10.1038/nbt.1873. http://www.hubmed.org/fulltext.cgi?uids=21633356

    Google Scholar 

  103. Kishore S, Jaskiewicz L, Burger L, Hausser J, Khorshid M, Zavolan M (2011) A quantitative analysis of CLIP methods for identifying binding sites of RNA–binding proteins. Nat Method 8(7):559–564. doi:10.1038/nmeth.1608. http://www.hubmed.org/fulltext.cgi?uids=21572407

  104. Corcoran DL, Georgiev S, Mukherjee N, Gottwein E, Skalsky RL, Keene JD, Ohler U (2011) PARalyzer: definition of RNA binding sites from PAR–CLIP short-read sequence data. Genome Biol 12(8). doi:10.1186/gb-2011-12-8-r79. http://www.hubmed.org/fulltext.cgi?uids=21851591

    Google Scholar 

  105. Hafner M, Landthaler M, Burger L, Khorshid M, Hausser J, Berninger P, Rothballer A, Ascano M Jr, Jungkamp A-C, Munschauer M, Ulrich A, Wardle GS, Dewell S, Zavolan M, Tuschl T (2010) Transcriptome-wide identification of RNA-binding protein and microRNA target sites by par-clip. Cell 141(1):129–141. doi:10.1016/j.cell.2010.03.009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  106. Silness J, Berge M (1990) Changes over time in the clientele and restoration pattern in a dental school prosthodontic department. Int Dent J 40(2):109–116

    CAS  PubMed  Google Scholar 

  107. Li X, Quon G, Lipshitz HD, Morris Q (2010) Predicting in vivo binding sites of RNA-binding proteins using mRNA secondary structure. RNA 16(6):1096–1107. doi:10.1261/rna.2017210. http://www.hubmed.org/fulltext.cgi?uids=20418358

  108. Georgiev S, Boyle AP, Jayasurya K, Ding X, Mukherjee S, Ohler U (2010) Evidence-ranked motif identification. Genome Biol 11(2):R19. doi:10.1186/gb-2010-11-2-r19

    Article  PubMed Central  PubMed  Google Scholar 

  109. Siddharthan R, Siggia ED, van Nimwegen E (2005) Phylogibbs: a gibbs sampling motif finder that incorporates phylogeny. PLoS Comput Biol 1(7):e67. doi:10.1371/journal.pcbi.0010067

    Article  PubMed Central  PubMed  Google Scholar 

  110. Zielinski J, Kilk K, Peritz T, Kannanayakal T, Miyashiro KY, Eiríksdóttir E, Jochems J, Langel U, Eberwine J (2006) In vivo identification of ribonucleoprotein-RNA interactions. Proc Natl Acad Sci USA 103(5):1557–1562. doi:10.1073/pnas.051 0611103. http://www.hubmed.org/fulltext.cgi?uids=16432185

    Google Scholar 

  111. Nielsen PE, Egholm M, Berg RH, Buchardt O (1991) Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 254(5037):1497–1500. http://www.hubmed.org/fulltext.cgi?uids=1962210

    Google Scholar 

  112. Butter F, Scheibe M, Mörl M, Mann M (2009) Unbiased RNA-protein interaction screen by quantitative proteomics. Proc Natl Acad Sci USA 106(26):10626–10631. doi:10.1073/pnas.0812099106. http://www.hubmed.org/fulltext.cgi?uids=19541640

    Google Scholar 

  113. Cook KB, Kazan H, Zuberi K, Morris Q, Hughes TR (2011) RBPDB: a database of RNA-binding specificities. Nucleic Acids Res 39(Database issue):301–308. doi:10.1093/nar/gkq1069. http://www.hubmed.org/fulltext.cgi?uids=21036867

  114. Khorshid M, Rodak C, Zavolan M (2011) Clipz: a database and analysis environment for experimentally determined binding sites of RNA-binding proteins. Nucleic Acids Res 39(Database issue):245–252. doi:10.1093/nar/gkq940. http://www.hubmed.org/fulltext.cgi?uids=21087992

  115. Lewis BA, Walia RR, Terribilini M, Ferguson J, Zheng C, Honavar V, Dobbs D (2011) PRIDB: a protein-RNA interface database. Nucleic Acids Res 39(Database issue):277–282. doi:10.1093/nar/gkq1108. http://www.hubmed.org/fulltext.cgi?uids=21071426

    Google Scholar 

  116. Allers J, Shamoo Y (2001) Structure-based analysis of protein-RNA interactions using the program entangle. J Mol Biol 311(1):75–86. doi:10.1006/jmbi.2001.4857

    Article  CAS  PubMed  Google Scholar 

  117. Sigrist CJ, Cerutti L, de Castro E, Langendijk-Genevaux PS, Bulliard V, Bairoch A, Hulo N (2010) Prosite, a protein domain database for functional characterization and annotation. Nucleic Acids Res 38(Database issue):D161–D166. doi:10.1093/nar/gkp885

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  118. Sarver M, Zirbel CL, Stombaugh J, Mokdad A, Leontis NB (2008) Fr3d: finding local and composite recurrent structural motifs in RNA 3D structures. J Math Biol 56(1–2):215–252. doi:10.1007/s00285-007-0110-x

    PubMed Central  PubMed  Google Scholar 

  119. Paradis E, Claude J, Strimmer K (2004) Ape: analyses of phylogenetics and evolution in R language. Bioinformatics 20(2):289–290. http://www.hubmed.org/fulltext.cgi?uids=14734327

    Google Scholar 

  120. Puton T, Kozlowski L, Tuszynska I, Rother K, Bujnicki JM (2011) Computational methods for prediction of protein-RNA interactions. J Struct Biol. doi:10.1016/j.jsb.2011.10.001

    PubMed  Google Scholar 

  121. Shulman-Peleg A, Shatsky M, Nussinov R, Wolfson HJ (2008) Prediction of interacting single-stranded RNA bases by protein-binding patterns. J Mol Biol 379(2):299–316. doi:10.1016/j.jmb.2008.03.043

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  122. Tompa M, Li N, Bailey TL, Church GM, De Moor B, Eskin E, Favorov AV, Frith MC, Fu Y, Kent WJ, Makeev VJ, Mironov AA, Noble WS, Pavesi G, Pesole G, Régnier M, Simonis N, Sinha S, Thijs G, van Helden J, Vandenbogaert M, Weng Z, Workman C, Ye C, Zhu Z (2005) Assessing computational tools for the discovery of transcription factor binding sites. Nat Biotechnol 23(1):137–144. doi:10.1038/nbt1053. http://www.hubmed.org/display.cgi?uids=15637633

    Google Scholar 

  123. Bailey TL, Elkan C (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 2:28–36. http://www.hubmed.org/display.cgi?uids=7584402

  124. Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, Lander ES, Kellis M (2005) Systematic discovery of regulatory motifs in human promoters and 3’ UTRs by comparison of several mammals. Nature 434(7031):338–345. doi:10.1038/nature03441

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  125. Hiller M, Pudimat R, Busch A, Backofen R (2006) Using RNA secondary structures to guide sequence motif finding towards single-stranded regions. Nucleic Acids Res 34(17). doi:10.1093/nar/gkl544. http://www.hubmed.org/fulltext.cgi?uids=16987907

  126. Bompfünewerer AF, Backofen R, Bernhart SH, Hertel J, Hofacker IL, Stadler PF, Will S (2008) Variations on RNA folding and alignment: lessons from benasque. J Math Biol 56(1–2):129–144. doi:10.1007/s00285-007-0107-5. http://www.hubmed.org/fulltext.cgi?uids=17611759

    Google Scholar 

  127. Pavesi G, Mauri G, Stefani M, Pesole G (2004) Rnaprofile: an algorithm for finding conserved secondary structure motifs in unaligned rna sequences. Nucleic Acids Res 32(10):3258–3269. doi:10.1093/nar/gkh650

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  128. Sankoff D (1985) Simultaneous solution of the RNA folding, alignment, and proto-sequence problems. SIAM J Appl Math 45:810–825

    Article  Google Scholar 

  129. Eddy SR, Durbin R (1994) RNA sequence analysis using covariance models. Nucleic Acids Res 22(11):2079–2088. http://www.hubmed.org/fulltext.cgi?uids=8029015

  130. Yao Z, Weinberg Z, Ruzzo WL (2006) Cmfinder–a covariance model based RNA motif finding algorithm. Bioinformatics 22(4):445–452. doi:10.1093/bioinformatics/btk008

    Article  CAS  PubMed  Google Scholar 

  131. Michal Rabani, Michael Kertesz, Eran Segal (2008) Computational prediction of RNA structural motifs involved in posttranscriptional regulatory processes. Proc Natl Acad Sci USA 105(39):14885–14890. doi:10.1073/pnas.0803169105

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  132. Foat BC, Houshmandi SS, Olivas WM, Bussemaker HJ (2005) Profiling condition-specific, genome-wide regulation of mRNA stability in yeast. Proc Natl Acad Sci USA 102(49):17675–17680. doi:10. 1073/pnas.0503803102. http://www.hubmed.org/fulltext.cgi?uids=16317069

    Google Scholar 

  133. Foat BC, Stormo GD (2009) Discovering structural cis-regulatory elements by modeling the behaviors of mRNAs. Mol Syst Biol 5:268–268. doi:10.1038/msb.2009.24. http://www.hubmed.org/fulltext.cgi?uids=19401680

    Google Scholar 

  134. Kazan H, Ray D, Chan ET, Hughes TR, Morris Q (2010) Rnacontext: a new method for learning the sequence and structure binding preferences of RNA-binding proteins. PLoS Comput Biol 6:e1000832. doi:10.1371/journal.pcbi.1000832

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

The preparation of this chapter was partially supported by a Canadian Institute of Health Research grant to Quaid Morris (MOP-93671) and by an Italian Autonomous Province of Trento grant to Angela Re.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Re, A., Joshi, T., Kulberkyte, E., Morris, Q., Workman, C.T. (2014). RNA–Protein Interactions: An Overview. In: Gorodkin, J., Ruzzo, W. (eds) RNA Sequence, Structure, and Function: Computational and Bioinformatic Methods. Methods in Molecular Biology, vol 1097. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-709-9_23

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-709-9_23

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-708-2

  • Online ISBN: 978-1-62703-709-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics