title: A physical and functional link between splicing factors promotes pre-mRNA 3' end processing.
abstract: Polypyrimidine tract-binding protein (PTB) is a splicing regulator that also plays a positive role in pre-mRNA 3' end processing when bound upstream of the polyadenylation signal (pA signal). Here, we address the mechanism of PTB stimulatory function in mRNA 3' end formation. We identify PTB as the protein factor whose binding to the human beta-globin (HBB) 3' UTR is abrogated by a 3' end processing-inactivating mutation. We show that PTB promotes both in vitro 3' end cleavage and polyadenylation and recruits directly the splicing factor hnRNP H to G-rich sequences associated with several pA signals. Increased binding of hnRNP H results in stimulation of polyadenylation through a direct interaction with poly(A) polymerase. Therefore, our results provide evidence of a concerted regulation of pA signal recognition by splicing factors bound to auxiliary polyadenylation sequence elements.
authors.affiliation: INSERM, U563, Toulouse, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300, France. stefania.millevoi@inserm.fr
authors.forename: Stefania
authors.initials: S
authors.lastname: Millevoi
authors.forename: Adrien
authors.initials: A
authors.lastname: Decorsière
authors.forename: Clarisse
authors.initials: C
authors.lastname: Loulergue
authors.forename: Jason
authors.initials: J
authors.lastname: Iacovoni
authors.forename: Sandra
authors.initials: S
authors.lastname: Bernat
authors.forename: Michael
authors.initials: M
authors.lastname: Antoniou
authors.forename: Stéphan
authors.initials: S
authors.lastname: Vagner
mesh_terms: D020413:3' Untranslated Regions / Q000737:chemistry; D001483:Base Sequence; D017124:Conserved Sequence; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000378:metabolism; D006801:Humans; D011061:Poly A / Q000378:metabolism; D026723:Polyadenylation; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D026721:RNA 3' End Processing; D012322:RNA Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D038621:Regulatory Sequences, Ribonucleic Acid; D055544:beta-Globins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D012322:RNA Precursors; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D055544:beta-Globins; D038941:Polypyrimidine Tract-Binding Protein; D011061:Poly A