Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-021-23615-w
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Funding
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- Institut Pasteur
- CNRS
- European Research Council (ERC) under the European Union [ERC-StG- 679243]
- Pasteur-Roux-Cantarini Postdoctoral Fellowship program
- Ligue Nationale Contre le Cancer [SFB19032]
- Region Ile-de-France
- Fondation pour la Recherche Medicale
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In this study, it was found that CSR-1 dependent 22G-RNAs are primarily produced in the cytosol on actively translating mRNAs, and the codon usage of an mRNA regulates the biogenesis of CSR-1 dependent 22G-RNAs.
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. 22G-RNAs are single-stranded antisense small RNAs that are expressed in C. elegans germline. Here the authors show that CSR-1 dependent 22G-RNAs are produced in the cytosol on mRNAs actively engaged in translation and that codon usage of an mRNA regulates the biogenesis of CSR-1 dependent 22G-RNAs.
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