Quantitative modeling of mRNA degradation reveals tempo-dependent mRNA clearance in early embryos.

As embryos transition from maternal to zygotic control, precise clearance of pre-loaded maternal mRNAs is essential for initiating new zygotic gene expression programs. Yet the kinetics of this process and how it adapts across different developmental speeds remain unclear. Here, we introduce QUANTA, a computational approach that uses time-series RNA-seq data to quantify mRNA turnover and polyadenylation dynamics of transcriptionally silent genes and find related regulatory motifs. Applying QUANTA to zebrafish, frog, mouse, and human embryos, we uncover a conserved regulatory logic: maternal mRNA degradation onset and rates align with species' developmental tempo. However, a subset of transcripts deviates from this pattern, suggesting species-specific kinetic tuning, which is further supported by the distinct use of destabilizing 3'UTR motifs in fast-developing species. Using temperature-based manipulation of zebrafish developmental speed and a high-throughput reporter assay, we reveal a regulatory logic of mRNA degradation scaling. Unstable mRNAs are not well-adapted to altered tempos, but scaling improves when enhancing stability through poly(A) tails or 3'UTR motifs. We demonstrate the tempo-sensitive function of 3'UTR motifs, linking regulatory sequences with developmental scaling. Our work establishes a quantitative framework for investigating mRNA turnover and reveals how clearance dynamics is tuned to match developmental pace.