TY - JOUR
T1 - A continuum of mRNP complexes in embryonic microRNA-mediated silencing
AU - Wu, Edlyn
AU - Vashisht, Ajay A.
AU - Chapat, Clément
AU - Flamand, Mathieu N.
AU - Cohen, Emiliano
AU - Sarov, Mihail
AU - Tabach, Yuval
AU - Sonenberg, Nahum
AU - Wohlschlegel, James
AU - Duchaine, Thomas F.
PY - 2017/2/28
Y1 - 2017/2/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85031868927&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/nar/gkw872
DO - https://doi.org/10.1093/nar/gkw872
M3 - Article
C2 - 28204614
SN - 0305-1048
VL - 45
SP - 2081
EP - 2098
JO - Nucleic acids research
JF - Nucleic acids research
IS - 4
ER -