U7 snRNP is recruited to histone pre-mRNA in a FLASH-dependent manner by two separate regions of the stem–loop binding protein

  1. Zbigniew Dominski1,4
  1. 1Integrative Program for Biological and Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
  2. 2Department of Biophysics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland
  3. 3Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
  4. 4Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
  1. Corresponding author: dominski{at}med.unc.edu

  • ↵5 Present address: Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294-1240, USA

Abstract

Cleavage of histone pre-mRNAs at the 3′ end requires stem–loop binding protein (SLBP) and U7 snRNP that consists of U7 snRNA and a unique Sm ring containing two U7-specific proteins: Lsm10 and Lsm11. Lsm11 interacts with FLASH and together they bring a subset of polyadenylation factors to U7 snRNP, including the CPSF73 endonuclease that cleaves histone pre-mRNA. SLBP binds to a conserved stem–loop structure upstream of the cleavage site and acts by promoting an interaction between the U7 snRNP and a sequence element located downstream from the cleavage site. We show that both human and Drosophila SLBPs stabilize U7 snRNP on histone pre-mRNA via two regions that are not directly involved in recognizing the stem–loop structure: helix B of the RNA binding domain and the C-terminal region that follows the RNA binding domain. Stabilization of U7 snRNP binding to histone pre-mRNA by SLBP requires FLASH but not the polyadenylation factors. Thus, FLASH plays two roles in 3′ end processing of histone pre-mRNAs: It interacts with Lsm11 to form a docking platform for the polyadenylation factors, and it cooperates with SLBP to recruit U7 snRNP to histone pre-mRNA.

Keywords

  • Received January 16, 2017.
  • Accepted March 9, 2017.

This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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  1. Published in Advance March 13, 2017, doi: 10.1261/rna.060806.117 RNA 23: 938-951 © 2017 Skrajna et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society

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