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A continuum of mRNP complexes in embryonic microRNA-mediated silencing

MicroRNAs (miRNAs) impinge on the translation and stability of their target mRNAs, and play key roles in development, homeostasis and disease. The gene regulation mechanisms they instigate are largely mediated through the CCR4–NOT deadenylase complex, but the molecular events that occur on target mR...

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Autores principales: Wu, Edlyn, Vashisht, Ajay A., Chapat, Clément, Flamand, Mathieu N., Cohen, Emiliano, Sarov, Mihail, Tabach, Yuval, Sonenberg, Nahum, Wohlschlegel, James, Duchaine, Thomas F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
RNA
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389717/
https://www.ncbi.nlm.nih.gov/pubmed/28204614
http://dx.doi.org/10.1093/nar/gkw872
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author Wu, Edlyn
Vashisht, Ajay A.
Chapat, Clément
Flamand, Mathieu N.
Cohen, Emiliano
Sarov, Mihail
Tabach, Yuval
Sonenberg, Nahum
Wohlschlegel, James
Duchaine, Thomas F.
author_facet Wu, Edlyn
Vashisht, Ajay A.
Chapat, Clément
Flamand, Mathieu N.
Cohen, Emiliano
Sarov, Mihail
Tabach, Yuval
Sonenberg, Nahum
Wohlschlegel, James
Duchaine, Thomas F.
author_sort Wu, Edlyn
collection PubMed
description MicroRNAs (miRNAs) impinge on the translation and stability of their target mRNAs, and play key roles in development, homeostasis and disease. The gene regulation mechanisms they instigate are largely mediated through the CCR4–NOT deadenylase complex, but the molecular events that occur on target mRNAs are poorly resolved. We observed a broad convergence of interactions of germ granule and P body mRNP components on AIN-1/GW182 and NTL-1/CNOT1 in Caenorhabditis elegans embryos. We show that the miRISC progressively matures on the target mRNA from a scanning form into an effector mRNP particle by sequentially recruiting the CCR4–NOT complex, decapping and decay, or germ granule proteins. Finally, we implicate intrinsically disordered proteins, key components in mRNP architectures, in the embryonic function of lsy-6 miRNA. Our findings define dynamic steps of effector mRNP assembly in miRNA-mediated silencing, and identify a functional continuum between germ granules and P bodies in the C. elegans embryo.
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spelling pubmed-53897172017-04-24 A continuum of mRNP complexes in embryonic microRNA-mediated silencing Wu, Edlyn Vashisht, Ajay A. Chapat, Clément Flamand, Mathieu N. Cohen, Emiliano Sarov, Mihail Tabach, Yuval Sonenberg, Nahum Wohlschlegel, James Duchaine, Thomas F. Nucleic Acids Res RNA MicroRNAs (miRNAs) impinge on the translation and stability of their target mRNAs, and play key roles in development, homeostasis and disease. The gene regulation mechanisms they instigate are largely mediated through the CCR4–NOT deadenylase complex, but the molecular events that occur on target mRNAs are poorly resolved. We observed a broad convergence of interactions of germ granule and P body mRNP components on AIN-1/GW182 and NTL-1/CNOT1 in Caenorhabditis elegans embryos. We show that the miRISC progressively matures on the target mRNA from a scanning form into an effector mRNP particle by sequentially recruiting the CCR4–NOT complex, decapping and decay, or germ granule proteins. Finally, we implicate intrinsically disordered proteins, key components in mRNP architectures, in the embryonic function of lsy-6 miRNA. Our findings define dynamic steps of effector mRNP assembly in miRNA-mediated silencing, and identify a functional continuum between germ granules and P bodies in the C. elegans embryo. Oxford University Press 2017-02-28 2016-10-03 /pmc/articles/PMC5389717/ /pubmed/28204614 http://dx.doi.org/10.1093/nar/gkw872 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle RNA
Wu, Edlyn
Vashisht, Ajay A.
Chapat, Clément
Flamand, Mathieu N.
Cohen, Emiliano
Sarov, Mihail
Tabach, Yuval
Sonenberg, Nahum
Wohlschlegel, James
Duchaine, Thomas F.
A continuum of mRNP complexes in embryonic microRNA-mediated silencing
title A continuum of mRNP complexes in embryonic microRNA-mediated silencing
title_full A continuum of mRNP complexes in embryonic microRNA-mediated silencing
title_fullStr A continuum of mRNP complexes in embryonic microRNA-mediated silencing
title_full_unstemmed A continuum of mRNP complexes in embryonic microRNA-mediated silencing
title_short A continuum of mRNP complexes in embryonic microRNA-mediated silencing
title_sort continuum of mrnp complexes in embryonic microrna-mediated silencing
topic RNA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389717/
https://www.ncbi.nlm.nih.gov/pubmed/28204614
http://dx.doi.org/10.1093/nar/gkw872
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