RRC ID 59566
Author Nousch M, Yeroslaviz A, Eckmann CR.
Title Stage-specific combinations of opposing poly(A) modifying enzymes guide gene expression during early oogenesis.
Journal Nucleic Acids Res
Abstract RNA-modifying enzymes targeting mRNA poly(A) tails are universal regulators of post-transcriptional gene expression programs. Current data suggest that an RNA-binding protein (RBP) directed tug-of-war between tail shortening and re-elongating enzymes operates in the cytoplasm to repress or activate specific mRNA targets. While this concept is widely accepted, it was primarily described in the final meiotic stages of frog oogenesis and relies molecularly on a single class of RBPs, i.e. CPEBs, the deadenylase PARN and cytoplasmic poly(A) polymerase GLD-2. Using the spatial and temporal resolution of female gametogenesis in the nematode C. elegans, we determined the distinct roles of known deadenylases throughout germ cell development and discovered that the Ccr4-Not complex is the main antagonist to GLD-2-mediated mRNA regulation. We find that the Ccr4-Not/GLD-2 balance is critical for essentially all steps of oocyte production and reiteratively employed by various classes of RBPs. Interestingly, its two deadenylase subunits appear to affect mRNAs stage specifically: while a Caf1/GLD-2 antagonism regulates mRNA abundance during all stages of oocyte production, a Ccr4/GLD-2 antagonism regulates oogenesis in an mRNA abundance independent manner. Our combined data suggests that the Ccr4-Not complex represents the evolutionarily conserved molecular opponent to GLD-2 providing an antagonistic framework of gene-specific poly(A)-tail regulation.
Volume 47(20)
Pages 10881-10893
Published 2019-11-18
DOI 10.1093/nar/gkz787
PII 5568212
PMID 31511882
PMC PMC6845980
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Differentiation Cell Proliferation Gene Expression Regulation, Developmental* Meiosis Oogenesis / genetics* Poly A / metabolism* Polyadenylation Prophase / genetics RNA Stability / genetics RNA, Messenger / genetics RNA, Messenger / metabolism Ribosomes / metabolism
IF 11.147
Times Cited 1
Resource
C.elegans tm1339 tm1575 tm1312 tm869