Spatio-temporally regulated maternal RNA decay factor essential for zebrafish development

Abstract

Maternal mRNA decay is essential for the Maternal-to-Zygotic Transition (MZT), yet its impact on spatial regulation has remained largely unexplored. We identify Cth1 as the first maternally encoded RNA-decay factor regulated in a spatiotemporal manner outside the germline in zebrafish, driven by conserved 3′UTR cis-elements. RfxCas13d-mediated depletion of maternal cth1 revealed early developmental defects that could not be assessed with SpyCas9 mutants due to infertility from impaired gametogenesis. Mechanistically, Cth1 acts independently of zygotic genome activation, recognizing AU-rich motifs in maternal 3′UTRs to promote deadenylation and decay in a spatio-temporal manner; deletion of these motifs or depletion of Cth1 stabilizes both reporter and endogenous transcripts. These findings establish Cth1 as a key component of the maternal program and provide the first direct evidence that spatio-temporally regulated mRNA decay, outside the germline, contributes to early vertebrate development. Highlights Cth1 is a highly deposited maternal mRNA that undergoes rapid decay 3’UTR of Cth1 drives its spatio-temporal dynamics. Cth1 is essential for gametogenesis and early embryonic development. CTH1 recognizes AU-rich elements in target 3′UTRs to trigger decay.