Ars2 Links the Nuclear Cap-Binding Complex to RNA Interference and Cell Proliferation

被引:163
作者
Gruber, Joshua J. [1 ,2 ]
Zatechka, D. Steven [3 ]
Sabin, Leah R. [4 ]
Yong, Jeongsik [5 ]
Lum, Julian J. [1 ,2 ]
Kong, Mei [1 ,2 ]
Zong, Wei-Xing [1 ,2 ]
Zhang, Zhenxi [5 ]
Lau, Chi-Kong [5 ]
Rawlings, Jason [3 ]
Cherry, Sara [4 ]
Ihle, James N. [3 ]
Dreyfuss, Gideon [5 ]
Thompson, Craig B. [1 ,2 ]
机构
[1] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Canc Biol, Philadelphia, PA 19104 USA
[3] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA
[4] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA
[5] Univ Penn, Sch Med, Howard Hughes Med Inst, Dept Biochem & Biophys, Philadelphia, PA 19104 USA
关键词
MESSENGER-RNA; PROTEOMIC ANALYSIS; PROTEIN; SERRATE; MICRORNAS; MIRNA; EXPORT; GENES;
D O I
10.1016/j.cell.2009.04.046
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:328 / 339
页数:12
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