Biology subjects

Ajaykumar, N.

Publications and source records attributed to Ajaykumar, N..

2 recordsLinked to original sources

bioRxiv2026

Divergent regulatory impacts of endogenous siRNAs on host mRNAs in testis of closely related species

Invertebrates use RNAi to fight viruses that replicate via dsRNA intermediates, which serve as precursors for producing anti-viral siRNAs. In addition, siRNAs are produced from a broad range of endogenous dsRNAs in Drosophila melanogaster. However, beyond the impacts of siRNAs derived from a handful of hairpin RNAs, the regulatory potential of most endo-siRNAs has been unknown. Here, we report that RNAi is far more potent in the close sister species Drosophila simulans. Consequently, endo-siRNAs repress less than a dozen transcripts in D. melanogaster, but hundreds of mRNAs in D. simulans testis. These regulatory interactions occur in cis (between pairs of bidirectionally transcribed loci), as well as in trans (between genomically unlinked siRNA-target pairs). We establish the molecular determinants of productive gene repression by siRNAs in vivo, including cleavage in trans via >16-nt contiguous complementarity. Our data indicate that D. simulans spermatogenesis requires repression of numerous host mRNAs by endo-siRNAs. More generally, we reveal unexpectedly fast-evolving and broad regulatory impacts of endogenous RNAi in the male germline.

molecular biology↗

bioRxiv2024

Mouse Pachytene piRNAs Cleave Hundreds of Transcripts,But Alter the Steady-State Abundance of Only a Minority of Targets

In animals, 18-35-nt piRNAs guide PIWI proteins to regulate complementary RNAs. During male meiosis, mammals produce an exceptionally abundant class of piRNAs called pachytene piRNAs. Pachytene piRNAs are required for spermatogenesis and have been proposed to control gene expression by various mechanisms. Here, we show that pachytene piRNAs regulate targets predominantly, if not exclusively, by endonucleolytic cleavage. Remarkably, pachytene piRNAs slice hundreds of RNAs, yet a change in steady-state level is detectable for a small fraction of transcripts. Our data suggest that cleavage of the few targets whose abundance is reduced significantly by piRNAs is essential for male fertility. Other pachytene piRNA targets are enriched for highly transcribed genes, which may explain why piRNA cleavage is often inconsequential for the steady-state abundance of targets. We propose that the retention of pachytene piRNAs throughout mammalian evolution is driven by the selective advantage conferred by a tiny minority of piRNAs.

molecular biology↗