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Translation and codon usage regulate Argonaute slicer activity to trigger germline small RNA biogenesis [RIP-Seq]

ABSTRACT: In 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 remain 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 concurrently with ribosome translation in the cytoplasm, in contrast to other 22G-RNAs mostly synthesized in germ-granules. Moreover, differences in germline mRNA codon optimality and ribosome occupancy antagonistically affect the abundance of CSR-1 22G-RNAs and the stability of their mRNA targets. We propose that codon usage differences encoded into mRNA sequences might be a conserved strategy adopted in eukaryotes to regulate small RNA biogenesis and Argonaute targeting.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE155075 | GEO | 2021/04/22

REPOSITORIES: GEO

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

Project description: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 ribosome translation in the cytoplasm, 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

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