U2 snRNP binds intronless histone pre-mRNAs to facilitate U7-snRNP-dependent 3' end formation

Mol Cell. 2007 Oct 26;28(2):240-52. doi: 10.1016/j.molcel.2007.09.026.

Abstract

In metazoa, pre-mRNA 3' end formation occurs via two pathways: cleavage/polyadenylation for the majority of RNA polymerase II transcripts and U7-snRNP-dependent cleavage for replication-dependent histone pre-mRNAs. An RNA element derived from a replication-dependent histone gene affects multiple steps of pre-mRNA processing. Here, we demonstrate that a portion of this RNA element, present in the majority of histone mRNAs, stimulates U7-snRNP-dependent cleavage. Surprisingly, this element binds U2 snRNP, although it is derived from an intronless mRNA. Specifically, SF3b, a U2 and U12-snRNP component, contacts the RNA element both in vitro and in vivo in conjunction with hPrp43, a DEAH-box helicase. Tethering either U2 or U12 snRNP to histone pre-mRNA substrates stimulates U7-snRNP-dependent cleavage in vitro and in vivo. Finally, we show that U2 snRNP associates with histone pre-mRNAs in vivo. We conclude that U2 snRNP plays a nonsplicing role in histone mRNA maturation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Cell Nucleus / metabolism*
  • DEAD-box RNA Helicases / metabolism
  • HeLa Cells
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Introns
  • Mice
  • Models, Molecular
  • Oocytes / metabolism
  • Protein Conformation
  • RNA 3' End Processing*
  • RNA Precursors / chemistry
  • RNA Precursors / metabolism*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism
  • Ribonucleoprotein, U2 Small Nuclear / chemistry
  • Ribonucleoprotein, U2 Small Nuclear / metabolism*
  • Ribonucleoprotein, U7 Small Nuclear / chemistry
  • Ribonucleoprotein, U7 Small Nuclear / metabolism*
  • Ribonucleoproteins, Small Nuclear / metabolism
  • Time Factors
  • Xenopus laevis

Substances

  • Histones
  • RNA Precursors
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoprotein, U2 Small Nuclear
  • Ribonucleoprotein, U7 Small Nuclear
  • Ribonucleoproteins, Small Nuclear
  • U11-U12 small nuclear ribonucleoprotein
  • DEAD-box RNA Helicases