Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis

Monika Srivastava; Guowen Duan; Nadia J. Kershaw; Vicki Athanasopoulos; Janet H.C. Yeo; Toyoyuki Ose; Desheng Hu; Simon H.J. Brown; Slobodan Jergic; Hardip R. Patel; Alvin Pratama; Sashika Richards; Anil Verma; E. Yvonne Jones; Vigo Heissmeyer; Thomas Preiss; Nicholas E. Dixon; Mark M.W. Chong; Jeffrey J. Babon; Carola G. Vinuesa

doi:10.1038/ncomms7253

Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis

Monika Srivastava, Guowen Duan, Nadia J. Kershaw, Vicki Athanasopoulos, Janet H.C. Yeo, Toyoyuki Ose, Desheng Hu, Simon H.J. Brown, Slobodan Jergic, Hardip R. Patel, Alvin Pratama, Sashika Richards, Anil Verma, E. Yvonne Jones, Vigo Heissmeyer, Thomas Preiss, Nicholas E. Dixon, Mark M.W. Chong, Jeffrey J. Babon, Carola G. Vinuesa^*

^*Corresponding author for this work

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

61 Citations (Scopus)

Abstract

Roquin is an RNA-binding protein that prevents autoimmunity and inflammation via repression of bound target mRNAs such as inducible costimulator (Icos). When Roquin is absent or mutated (Roquin^san), Icos is overexpressed in T cells. Here we show that Roquin enhances Dicer-mediated processing of pre-miR-146a. Roquin also directly binds Argonaute2, a central component of the RNA-induced silencing complex, and miR-146a, a microRNA that targets Icos mRNA. In the absence of functional Roquin, miR-146a accumulates in T cells. Its accumulation is not due to increased transcription or processing, rather due to enhanced stability of mature miR-146a. This is associated with decreased 3′ end uridylation of the miRNA. Crystallographic studies reveal that Roquin contains a unique HEPN domain and identify the structural basis of the 'san' mutation and Roquin's ability to bind multiple RNAs. Roquin emerges as a protein that can bind Ago2, miRNAs and target mRNAs, to control homeostasis of both RNA species.

Original language	English
Article number	6253
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7253
Publication status	Published - 20 Feb 2015

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Srivastava, M., Duan, G., Kershaw, N. J., Athanasopoulos, V., Yeo, J. H. C., Ose, T., Hu, D., Brown, S. H. J., Jergic, S., Patel, H. R., Pratama, A., Richards, S., Verma, A., Jones, E. Y., Heissmeyer, V., Preiss, T., Dixon, N. E., Chong, M. M. W., Babon, J. J., & Vinuesa, C. G. (2015). Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis. Nature Communications, 6, Article 6253. https://doi.org/10.1038/ncomms7253

@article{af897088f247460e9e8f08cb18c6b64f,

title = "Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis",

abstract = "Roquin is an RNA-binding protein that prevents autoimmunity and inflammation via repression of bound target mRNAs such as inducible costimulator (Icos). When Roquin is absent or mutated (Roquinsan), Icos is overexpressed in T cells. Here we show that Roquin enhances Dicer-mediated processing of pre-miR-146a. Roquin also directly binds Argonaute2, a central component of the RNA-induced silencing complex, and miR-146a, a microRNA that targets Icos mRNA. In the absence of functional Roquin, miR-146a accumulates in T cells. Its accumulation is not due to increased transcription or processing, rather due to enhanced stability of mature miR-146a. This is associated with decreased 3′ end uridylation of the miRNA. Crystallographic studies reveal that Roquin contains a unique HEPN domain and identify the structural basis of the 'san' mutation and Roquin's ability to bind multiple RNAs. Roquin emerges as a protein that can bind Ago2, miRNAs and target mRNAs, to control homeostasis of both RNA species.",

author = "Monika Srivastava and Guowen Duan and Kershaw, {Nadia J.} and Vicki Athanasopoulos and Yeo, {Janet H.C.} and Toyoyuki Ose and Desheng Hu and Brown, {Simon H.J.} and Slobodan Jergic and Patel, {Hardip R.} and Alvin Pratama and Sashika Richards and Anil Verma and Jones, {E. Yvonne} and Vigo Heissmeyer and Thomas Preiss and Dixon, {Nicholas E.} and Chong, {Mark M.W.} and Babon, {Jeffrey J.} and Vinuesa, {Carola G.}",

note = "Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

year = "2015",

month = feb,

day = "20",

doi = "10.1038/ncomms7253",

language = "English",

volume = "6",

journal = "Nature Communications",

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Srivastava, M, Duan, G, Kershaw, NJ, Athanasopoulos, V, Yeo, JHC, Ose, T, Hu, D, Brown, SHJ, Jergic, S, Patel, HR, Pratama, A, Richards, S, Verma, A, Jones, EY, Heissmeyer, V, Preiss, T, Dixon, NE, Chong, MMW, Babon, JJ & Vinuesa, CG 2015, 'Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis', Nature Communications, vol. 6, 6253. https://doi.org/10.1038/ncomms7253

TY - JOUR

T1 - Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis

AU - Srivastava, Monika

AU - Duan, Guowen

AU - Kershaw, Nadia J.

AU - Athanasopoulos, Vicki

AU - Yeo, Janet H.C.

AU - Ose, Toyoyuki

AU - Hu, Desheng

AU - Brown, Simon H.J.

AU - Jergic, Slobodan

AU - Patel, Hardip R.

AU - Pratama, Alvin

AU - Richards, Sashika

AU - Verma, Anil

AU - Jones, E. Yvonne

AU - Heissmeyer, Vigo

AU - Preiss, Thomas

AU - Dixon, Nicholas E.

AU - Chong, Mark M.W.

AU - Babon, Jeffrey J.

AU - Vinuesa, Carola G.

PY - 2015/2/20

Y1 - 2015/2/20

N2 - Roquin is an RNA-binding protein that prevents autoimmunity and inflammation via repression of bound target mRNAs such as inducible costimulator (Icos). When Roquin is absent or mutated (Roquinsan), Icos is overexpressed in T cells. Here we show that Roquin enhances Dicer-mediated processing of pre-miR-146a. Roquin also directly binds Argonaute2, a central component of the RNA-induced silencing complex, and miR-146a, a microRNA that targets Icos mRNA. In the absence of functional Roquin, miR-146a accumulates in T cells. Its accumulation is not due to increased transcription or processing, rather due to enhanced stability of mature miR-146a. This is associated with decreased 3′ end uridylation of the miRNA. Crystallographic studies reveal that Roquin contains a unique HEPN domain and identify the structural basis of the 'san' mutation and Roquin's ability to bind multiple RNAs. Roquin emerges as a protein that can bind Ago2, miRNAs and target mRNAs, to control homeostasis of both RNA species.

AB - Roquin is an RNA-binding protein that prevents autoimmunity and inflammation via repression of bound target mRNAs such as inducible costimulator (Icos). When Roquin is absent or mutated (Roquinsan), Icos is overexpressed in T cells. Here we show that Roquin enhances Dicer-mediated processing of pre-miR-146a. Roquin also directly binds Argonaute2, a central component of the RNA-induced silencing complex, and miR-146a, a microRNA that targets Icos mRNA. In the absence of functional Roquin, miR-146a accumulates in T cells. Its accumulation is not due to increased transcription or processing, rather due to enhanced stability of mature miR-146a. This is associated with decreased 3′ end uridylation of the miRNA. Crystallographic studies reveal that Roquin contains a unique HEPN domain and identify the structural basis of the 'san' mutation and Roquin's ability to bind multiple RNAs. Roquin emerges as a protein that can bind Ago2, miRNAs and target mRNAs, to control homeostasis of both RNA species.

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U2 - 10.1038/ncomms7253

DO - 10.1038/ncomms7253

M3 - Article

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 6253

ER -

Roquin binds microRNA-146a and Argonaute2 to regulate microRNA homeostasis

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