Year: 2026
Type: preprint
Abstract: The spatiotemporal expression patterns of microRNAs (miRNAs) are crucial to their function. Target-directed miRNA degradation (TDMD) is an emerging regulatory module that contributes to these expression patterns wherein a specialized RNA (TDMD trigger) drives miRNA decay through base pairing and resulting recruitment of E3 ubiquitin ligase ZSWIM8/EBAX-1. Extensive base pairing to the miRNA seed region and 3’ end has been proposed as a key feature that distinguishes TDMD triggers from conventional mRNA targets of miRNAs, which primarily pair with the seed. Here we identify the long noncoding RNA, tts-2 , as a TDMD trigger for mir-35-42 , the most abundant miRNA family in C. elegans early embryos. We demonstrate that a single site in tts-2 drives decay through base pairing with the seed sequence shared by all eight family members. A second site in tts-2 supports decay of mir-38 with incomplete seed complementarity. Our findings demonstrate that extended base pairing is not a universal requirement for TDMD, and that TDMD drives developmentally-timed clearance of abundant miRNAs at the exit of C. elegans embryogenesis.
Source: Genes & Development
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Funders: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W7134136991