A lncRNA drives developmentally-timed decay of all members an essential microRNA family

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. Here we show a long noncoding RNA, tts-2, drives developmentally-timed TDMD of mir-35-42, representing a large-scale resetting of the miRNA pool at the end of embryogenesis in C. elegans.

While extensive base pairing to the miRNA seed and 3′ end was thought to be the distinguishing feature of TDMD triggers, a single site in tts-2 drives decay of mir-35-42 through base pairing to the seed region. A second unusual site supports decay of mir-38 with incomplete seed complementarity. The relaxed base pairing requirements of tts-2-induced TDMD demonstrate that alternative cues – not just extensive miRNA 3′ end pairing – can license transcripts to drive TDMD.