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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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Detalles Bibliográficos
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
Descripción
Sumario: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.