Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation.
Here we identify a component of the nuclear RNA cap-binding complex (CBC), Ars2, that is important for miRNA biogenesis and critical for cell proliferation. Unlike other components of the CBC, Ars2 expression is linked to the proliferative state of the cell. Deletion of Ars2 is developmentally lethal, and deletion in adult mice led to bone marrow failure whereas parenchymal organs composed of nonproliferating cells were unaffected. Depletion of Ars2 or CBP80 from proliferating cells impaired miRNA-mediated repression and led to alterations in primary miRNA processing in the nucleus. Ars2 depletion also reduced the levels of several miRNAs, including miR-21, let-7, and miR-155, that are implicated in cellular transformation. These findings provide evidence for a role for Ars2 in RNA interference regulation during cell proliferation.
Gruber
Joshua J
JJ
Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zatechka
D Steven
DS
Sabin
Leah R
LR
Yong
Jeongsik
J
Lum
Julian J
JJ
Kong
Mei
M
Zong
Wei-Xing
WX
Zhang
Zhenxi
Z
Lau
Chi-Kong
CK
Rawlings
Jason
J
Cherry
Sara
S
Ihle
James N
JN
Dreyfuss
Gideon
G
Thompson
Craig B
CB
D000818:Animals; D001151:Arsenic / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs; D039502:Nuclear Cap-Binding Protein Complex / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D034622:RNA Interference
D035683:MicroRNAs; D039502:Nuclear Cap-Binding Protein Complex; D009687:Nuclear Proteins; D006151:Guanosine; C016578:7-methylguanosine; D001151:Arsenic