TY - JOUR
T1 - The human cap-binding complex is functionally connected to the nuclear RNA exosome
AU - Andersen, Peter Refsing
AU - Domanski, Michal
AU - Kristiansen, Maiken S
AU - Storvall, Helena
AU - Ntini, Evgenia
AU - Verheggen, Celine
AU - Schein, Aleks
AU - Bunkenborg, Jakob
AU - Poser, Ina
AU - Hallais, Marie
AU - Sandberg, Rickard
AU - Hyman, Anthony
AU - Lacava, John
AU - Rout, Michael P
AU - Andersen, Jens Sandberg
AU - Bertrand, Edouard
AU - Jensen, Torben Heick
PY - 2013/11/24
Y1 - 2013/11/24
N2 - Nuclear processing and quality control of eukaryotic RNA is mediated by the RNA exosome, which is regulated by accessory factors. However, the mechanism of exosome recruitment to its ribonucleoprotein (RNP) targets remains poorly understood. Here we report a physical link between the human exosome and the cap-binding complex (CBC). The CBC associates with the ARS2 protein to form CBC-ARS2 (CBCA) and then further connects, together with the ZC3H18 protein, to the nuclear exosome targeting (NEXT) complex, thus forming CBC-NEXT (CBCN). RNA immunoprecipitation using CBCN factors as well as the analysis of combinatorial depletion of CBCN and exosome components underscore the functional relevance of CBC-exosome bridging at the level of target RNA. Specifically, CBCA suppresses read-through products of several RNA families by promoting their transcriptional termination. We suggest that the RNP 5' cap links transcription termination to exosomal RNA degradation through CBCN.
AB - Nuclear processing and quality control of eukaryotic RNA is mediated by the RNA exosome, which is regulated by accessory factors. However, the mechanism of exosome recruitment to its ribonucleoprotein (RNP) targets remains poorly understood. Here we report a physical link between the human exosome and the cap-binding complex (CBC). The CBC associates with the ARS2 protein to form CBC-ARS2 (CBCA) and then further connects, together with the ZC3H18 protein, to the nuclear exosome targeting (NEXT) complex, thus forming CBC-NEXT (CBCN). RNA immunoprecipitation using CBCN factors as well as the analysis of combinatorial depletion of CBCN and exosome components underscore the functional relevance of CBC-exosome bridging at the level of target RNA. Specifically, CBCA suppresses read-through products of several RNA families by promoting their transcriptional termination. We suggest that the RNP 5' cap links transcription termination to exosomal RNA degradation through CBCN.
U2 - 10.1038/nsmb.2703
DO - 10.1038/nsmb.2703
M3 - Journal article
C2 - 24270879
SN - 1545-9993
VL - 20
SP - 1367
EP - 1376
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 12
ER -