title: U2 snRNP binds intronless histone pre-mRNAs to facilitate U7-snRNP-dependent 3' end formation.
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.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Friend
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Lovejoy
authors.forename: Joan A
authors.initials: JA
authors.lastname: Steitz
mesh_terms: D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007438:Introns; D051379:Mice; D008958:Models, Molecular; D009865:Oocytes / Q000378:metabolism; D011487:Protein Conformation; D026721:RNA 3' End Processing; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000737:chemistry / Q000378:metabolism*; D020885:Ribonucleoprotein, U7 Small Nuclear / Q000737:chemistry / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism; D013997:Time Factors; D014982:Xenopus laevis
chemical_list: D006657:Histones; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; D020885:Ribonucleoprotein, U7 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; C552126:U11-U12 small nuclear ribonucleoprotein; D053487:DEAD-box RNA Helicases