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PMID: 19632182 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation.

Cell ·Vol. 138 ·No. 2 ·2009-07-23 ·Pages 328-39

Gruber JJ, Zatechka DS, Sabin LR, Yong J, Lum JJ, Kong M, Zong WX, Zhang Z, Lau CK, Rawlings J, Cherry S, Ihle JN, Dreyfuss G, Thompson CB

Abstract

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.

MeSH Terms
Animals Arsenic/toxicity Cell Line Cell Proliferation Guanosine/analogs & derivatives,metabolism Humans Mice MicroRNAs Nuclear Cap-Binding Protein Complex/metabolism Nuclear Proteins/metabolism RNA Interference
Chemicals
MicroRNAs Nuclear Cap-Binding Protein Complex Nuclear Proteins Guanosine 7-methylguanosine Arsenic
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Gruber Joshua J
Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zatechka D Steven
Sabin Leah R
Yong Jeongsik
Lum Julian J
Kong Mei
Zong Wei-Xing
Zhang Zhenxi
Lau Chi-Kong
Rawlings Jason
Cherry Sara
Ihle James N
Dreyfuss Gideon
Thompson Craig B
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.04.046
Published
2009-07-23
Pages
328-39
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2717034
Subset
IM
Grants
NCI NIH HHS · K01 CA098092-02 · United States
NCI NIH HHS · K01 CA098092-06 · United States
Howard Hughes Medical Institute · United States
NCI NIH HHS · K01 CA098092-03 · United States
NCI NIH HHS · K01 CA098092-04 · United States
NCI NIH HHS · K01 CA098092 · United States
NCI NIH HHS · R01 CA099179 · United States
NCI NIH HHS · R01 CA092660-09 · United States
NCI NIH HHS · R01 CA099179-07 · United States
NCI NIH HHS · K01 CA098092-05 · United States
NCI NIH HHS · R01 CA092660 · United States
NCI NIH HHS · K01 CA098092-01A2 · United States
Corrections
CommentIn
PMID: 19632172
External Links
PubMed source DOI: 10.1016/j.cell.2009.04.046 PMC Full Text View journal details
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