Novel long noncoding RNA lnc_2217 regulates zygotic genome activation through miR-877-3p/YTHDF2 pathway in goat

Abstract

Precisely timed zygotic genome activation (ZGA) and controlled maternal mRNA decay are critical for early embryo development in mammals. Although long non-coding RNA (lncRNAs) have been reported to regulate the early embryo development, their roles remain unclear during ZGA. Here we show that novel lncRNA lnc_2217 is indispensable for the early embryo development as microinjection of siRNAs against lnc_2217 reduced blastocyst formation from 32.5 % to 13.9 % and increased developmental arrest at the 8- and 16-cell stages. RNA-seq and 5-EU incorporation assays revealed that lnc_2217 knockdown impaired global de-novo transcription and provoked over-degradation of maternal mRNAs at the 8-cell stage. Mechanistically, lnc_2217 functions as a competing endogenous RNA that sequesters miR-877-3p, thereby relieving repression of the m6A reader YTHDF2. Loss of lnc_2217 leads to YTHDF2 down-regulation and accelerated turnover of key maternal transcripts (ZAR1, YAP1, UHRF1). Our findings identify an lnc_2217/miR-877-3p/YTHDF2 axis that synchronizes transcriptional activation with selective maternal mRNA clearance during ZGA, highlighting lnc_2217 as a crucial regulator of early goat embryogenesis.