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.
CBC-ARS2 stimulates 3′-end maturation of multiple RNA families and favors cap-proximal processing
Hallais, M.; Pontvianne, F.; Andersen, P. R.; Clerici, M.; Lener, D.; Benbahouche Nel, H.; Gostan, T.; Vandermoere, F.; Robert, M. C.; Cusack, S.; Verheggen, C.; Jensen, T. H.; Bertrand, E.
Nat Struct Mol Biol
2013-12 / vol 20 / pages 1358-66
10.1038/nsmb.2720 nsmb.2720 [pii]
1545-9985 (Electronic) 1545-9985 (Linking)