TY - JOUR
T1 - CBC-ARS2 stimulates 3'-end maturation of multiple RNA families and favors cap-proximal processing
AU - Hallais, Marie
AU - Pontvianne, Frédéric
AU - Andersen, Peter Refsing
AU - Clerici, Marcello
AU - Lener, Daniela
AU - Benbahouche, Nour El Houda
AU - Gostan, Thierry
AU - Vandermoere, Franck
AU - Robert, Marie-Cécile
AU - Cusack, Stephen
AU - Verheggen, Céline
AU - Jensen, Torben Heick
AU - Bertrand, Edouard
PY - 2013/11/24
Y1 - 2013/11/24
N2 - 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.
AB - 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.
U2 - 10.1038/nsmb.2720
DO - 10.1038/nsmb.2720
M3 - Journal article
C2 - 24270878
SN - 1545-9993
VL - 20
SP - 1358
EP - 1366
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 12
ER -