In vitro methylation of the U7 snRNP subunits Lsm11 and SmE by the PRMT5/MEP50/pICln methylosome
- Xiao-cui Yang1,6,
- Anthony Desotell2,6,
- Min-Han Lin2,6,
- Andrew S. Paige2,6,
- Agata Malinowska3,
- Yadong Sun2,7,
- Wei Shen Aik2,8,
- Michał Dadlez3,4,
- Liang Tong2 and
- Zbigniew Dominski1,5
- 1Integrative Program for Biological and Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
- 2Department of Biological Sciences, Columbia University, New York, New York 10027, USA
- 3Department of Biophysics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland
- 4Institute of Genetics and Biotechnology, Warsaw University, 02-106 Warsaw, Poland
- 5Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
- Corresponding authors: dominski{at}med.unc.edu, ltong{at}columbia.edu
-
↵6 These authors contributed equally to this work.
Abstract
U7 snRNP is a multisubunit endonuclease required for 3′ end processing of metazoan replication-dependent histone pre-mRNAs. In contrast to the spliceosomal snRNPs, U7 snRNP lacks the Sm subunits D1 and D2 and instead contains two related proteins, Lsm10 and Lsm11. The remaining five subunits of the U7 heptameric Sm ring, SmE, F, G, B, and D3, are shared with the spliceosomal snRNPs. The pathway that assembles the unique ring of U7 snRNP is unknown. Here, we show that a heterodimer of Lsm10 and Lsm11 tightly interacts with the methylosome, a complex of the arginine methyltransferase PRMT5, MEP50, and pICln known to methylate arginines in the carboxy-terminal regions of the Sm proteins B, D1, and D3 during the spliceosomal Sm ring assembly. Both biochemical and cryo-EM structural studies demonstrate that the interaction is mediated by PRMT5, which binds and methylates two arginine residues in the amino-terminal region of Lsm11. Surprisingly, PRMT5 also methylates an amino-terminal arginine in SmE, a subunit that does not undergo this type of modification during the biogenesis of the spliceosomal snRNPs. An intriguing possibility is that the unique methylation pattern of Lsm11 and SmE plays a vital role in the assembly of the U7 snRNP.
Keywords
- Received May 10, 2023.
- Accepted July 8, 2023.
This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
