PgmNr W456: A continuum of mRNP complexes in embryonic miRNA-mediated silencing.

Authors:
Thomas Duchaine 1 ; Edlyn Wu 1 ; Ajay Vashisht 2 ; Clément Chapat 1 ; Mathieu Flamand 1 ; Emiliano Cohen 3 ; Mihail Sarov 4 ; Yuval Tabach 3 ; Nahum Sonenberg 1 ; James Wohlschlegel 2


Institutes
1) Department of Biochemistry and Goodman Cancer Research Centre, McGill Univ., Montreal, Quebec, Canada; 2) Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 3) Hebrew Univ., Hadassah Medical School, Jerusalem, Israel; 4) Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.


Keyword: microRNA biogenesis and function

Abstract:

MicroRNAs (miRNAs) impinge on the translation and stability of a wide variety of mRNAs, and play key roles in development, homeostasis and disease. The gene regulation mechanisms they instigate are largely effected through the activities and interactions of the CCR4-NOT deadenylase complex, but the molecular events that occur on target mRNAs and lead to silencing are poorly resolved. Using comparative proteomics, we observed a broad convergence of interactions of germ granule and P body mRNP components on AIN-1/GW182 and NTL-1/CNOT1 in the C. elegans embryo. 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, and mRNP components such as the decapping and decay, or germ granule proteins. Finally, we provide evidence for a role of intrinsically disordered proteins in embryonic miRNA-mediated silencing. Our findings define dynamic steps of effector mRNP assembly in embryonic miRNA-mediated silencing, and identify a functional continuum between germ granules and P bodies in the C. elegans embryo.



Wormbase Genetic Index
1. ntl-1
2. ain-1
3. alg-2