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© Germano Cecere, Institut Pasteur
Publication : Nature communications

Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 09 Jun 2021

Singh M, Cornes E, Li B, Quarato P, Bourdon L, Dingli F, Loew D, Proccacia S, Cecere G,

Link to Pubmed [PMID] – 34108460

Link to DOI – 10.1038/s41467-021-23615-w

Nat Commun 2021 06; 12(1): 3492

In the Caenorhabditis elegans germline, thousands of mRNAs are concomitantly expressed with antisense 22G-RNAs, which are loaded into the Argonaute CSR-1. Despite their essential functions for animal fertility and embryonic development, how CSR-1 22G-RNAs are produced remains unknown. Here, we show that CSR-1 slicer activity is primarily involved in triggering the synthesis of small RNAs on the coding sequences of germline mRNAs and post-transcriptionally regulates a fraction of targets. CSR-1-cleaved mRNAs prime the RNA-dependent RNA polymerase, EGO-1, to synthesize 22G-RNAs in phase with translating ribosomes, in contrast to other 22G-RNAs mostly synthesized in germ granules. Moreover, codon optimality and efficient translation antagonize CSR-1 slicing and 22G-RNAs biogenesis. We propose that codon usage differences encoded into mRNA sequences might be a conserved strategy in eukaryotes to regulate small RNA biogenesis and Argonaute targeting.