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

Joshua J. Gruber; D. Steven Zatechka; Leah R. Sabin; Jeongsik Yong; Julian J. Lum; Mei Kong; Wei Xing Zong; Zhenxi Zhang; Chi Kong Lau; Jason Rawlings; Sara Cherry; James N. Ihle; Gideon Dreyfuss; Craig B. Thompson

doi:10.1016/j.cell.2009.04.046

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

Joshua J. Gruber, D. Steven Zatechka, Leah R. Sabin, Jeongsik Yong, Julian J. Lum, Mei Kong, Wei Xing Zong, Zhenxi Zhang, Chi Kong Lau, Jason Rawlings, Sara Cherry, James N. Ihle, Gideon Dreyfuss, Craig B. Thompson

Research output: Contribution to journal › Article › peer-review

167 Scopus citations

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.

Original language	English (US)
Pages (from-to)	328-339
Number of pages	12
Journal	Cell
Volume	138
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2009.04.046
State	Published - Jul 23 2009
Externally published	Yes

Keywords

CELLCYCLE
RNA

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2009.04.046

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@article{0aac89d8889441d792f1e5767a33a4b7,

title = "Ars2 Links the Nuclear Cap-Binding Complex to RNA Interference and Cell Proliferation",

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.",

keywords = "CELLCYCLE, RNA",

author = "Gruber, {Joshua J.} and Zatechka, {D. Steven} and Sabin, {Leah R.} and Jeongsik Yong and Lum, {Julian J.} and Mei Kong and Zong, {Wei Xing} and Zhenxi Zhang and Lau, {Chi Kong} and Jason Rawlings and Sara Cherry and Ihle, {James N.} and Gideon Dreyfuss and Thompson, {Craig B.}",

note = "Funding Information: We thank Zissimos Mourelatos for helpful discussions and providing luciferase reporters. We thank Iain Mattaj for kindly providing CBC antibodies, Ramin Shiekhattar for kindly providing Flag-Dicer and Flag-Drosha plasmids, and Michael Milone for providing a pri-miR-155 plasmid. We thank Jim Alwine, Scott Poethig, and members of the Thompson and Dreyfuss laboratories for discussions and inspiration. J.J.G. and C.B.T. are supported by funds from the NIH and the A.F.C.R.I. ",

year = "2009",

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doi = "10.1016/j.cell.2009.04.046",

language = "English (US)",

volume = "138",

pages = "328--339",

journal = "Cell",

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T1 - Ars2 Links the Nuclear Cap-Binding Complex to RNA Interference and Cell Proliferation

AU - Gruber, Joshua J.

AU - Zatechka, D. Steven

AU - Sabin, Leah R.

AU - Yong, Jeongsik

AU - Lum, Julian J.

AU - Kong, Mei

AU - Zong, Wei Xing

AU - Zhang, Zhenxi

AU - Lau, Chi Kong

AU - Rawlings, Jason

AU - Cherry, Sara

AU - Ihle, James N.

AU - Dreyfuss, Gideon

AU - Thompson, Craig B.

N1 - Funding Information: We thank Zissimos Mourelatos for helpful discussions and providing luciferase reporters. We thank Iain Mattaj for kindly providing CBC antibodies, Ramin Shiekhattar for kindly providing Flag-Dicer and Flag-Drosha plasmids, and Michael Milone for providing a pri-miR-155 plasmid. We thank Jim Alwine, Scott Poethig, and members of the Thompson and Dreyfuss laboratories for discussions and inspiration. J.J.G. and C.B.T. are supported by funds from the NIH and the A.F.C.R.I.

PY - 2009/7/23

Y1 - 2009/7/23

N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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