Arginine methylation promotes siRNA-binding specificity for a spermatogenesis-specific isoform of the Argonaute protein CSR-1

• Published in: Nature communications Vol. 12; no. 1; p. 4212
• Main Authors: Nguyen, Dieu An H., Phillips, Carolyn M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 09.07.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Binding; Developmental stages; DNA methylation; Fertility; Gene mapping; Genes; Germ cells; Isoforms; Localization; Mapping; Methylation; Oogenesis; Proteins; Regulatory mechanisms (biology); Ribonucleic acid; RNA; siRNA; Spatial discrimination; Spermatogenesis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-24526-6

Abstract CSR-1 is an essential Argonaute protein that binds to a subclass of 22G-RNAs targeting most germline-expressed genes. Here we show that the two isoforms of CSR-1 have distinct expression patterns; CSR-1B is ubiquitously expressed throughout the germline and during all stages of development while CSR-1A expression is restricted to germ cells undergoing spermatogenesis. Furthermore, CSR-1A associates preferentially with 22G-RNAs mapping to spermatogenesis-specific genes whereas CSR-1B-bound small RNAs map predominantly to oogenesis-specific genes. Interestingly, the exon unique to CSR-1A contains multiple dimethylarginine modifications, which are necessary for the preferential binding of CSR-1A to spermatogenesis-specific 22G-RNAs. Thus, we have discovered a regulatory mechanism for C. elegans Argonaute proteins that allows for specificity of small RNA binding between similar Argonaute proteins with overlapping temporal and spatial localization.