title: CBC-ARS2 stimulates 3'-end maturation of multiple RNA families and favors cap-proximal processing.
abstract: The nuclear cap-binding complex (CBC) stimulates multiple steps in several RNA maturation pathways, but how it functions in humans is incompletely understood. For small, capped RNAs such as pre-snRNAs, the CBC recruits PHAX. Here, we identify the CBCAP complex, composed of CBC, ARS2 and PHAX, and show that both CBCAP and CBC-ARS2 complexes can be reconstituted from recombinant proteins. ARS2 stimulates PHAX binding to the CBC and snRNA 3'-end processing, thereby coupling maturation with export. In vivo, CBC and ARS2 bind similar capped noncoding and coding RNAs and stimulate their 3'-end processing. The strongest effects are for cap-proximal polyadenylation sites, and this favors premature transcription termination. ARS2 functions partly through the mRNA 3'-end cleavage factor CLP1, which binds RNA Polymerase II through PCF11. ARS2 is thus a major CBC effector that stimulates functional and cryptic 3'-end processing sites.
authors.affiliation: Equipe labellisée Ligue contre le Cancer, Institut de Génétique Moléculaire de Montpellier-Centre National de la Recherche Scientifique, Montpellier, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Hallais
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pontvianne
authors.forename: Peter Refsing
authors.initials: PR
authors.lastname: Andersen
authors.forename: Marcello
authors.initials: M
authors.lastname: Clerici
authors.forename: Daniela
authors.initials: D
authors.lastname: Lener
authors.forename: Nour El Houda
authors.initials: Nel H
authors.lastname: Benbahouche
authors.forename: Thierry
authors.initials: T
authors.lastname: Gostan
authors.forename: Franck
authors.initials: F
authors.lastname: Vandermoere
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Robert
authors.forename: Stephen
authors.initials: S
authors.lastname: Cusack
authors.forename: Céline
authors.initials: C
authors.lastname: Verheggen
authors.forename: Torben Heick
authors.initials: TH
authors.lastname: Jensen
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
mesh_terms: D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D039502:Nuclear Cap-Binding Protein Complex / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011061:Poly A / Q000737:chemistry / Q000378:metabolism; D026721:RNA 3' End Processing
chemical_list: D039502:Nuclear Cap-Binding Protein Complex; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; C498688:PHAX protein, human; D010750:Phosphoproteins; C527299:SRRT protein, human; D011061:Poly A