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

Meetali Singh (1) , Eric Cornes (1) , Blaise Li (1, 2) , Piergiuseppe Quarato (1, 3) , Loan Bourdon (1) , Florent Dingli (4) , Damarys Loew (4) , Simone Proccacia (1, 5) , Germano Cecere (1)

1 Mécanismes de l'Hérédité épigénétique / Mechanisms of epigenetic inheritance
2 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
3 Collège Doctoral
4 Laboratoire de Spectrométrie de Masse Protéomique
5 University of Trento [Trento]

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.

Domains: Development Biology

Meetali Singh, Eric Cornes, Blaise Li, Piergiuseppe Quarato, Loan Bourdon, et al.. Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis. Nature Communications, 2021, 12 (1), pp.3492. ⟨10.1038/s41467-021-23615-w⟩. ⟨pasteur-03258520⟩