Genome wide analysis of 3’-UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish: Developmental mRNA-seq timecourse

Post-transcriptional regulation plays a crucial role in shaping gene expression. During the Maternal-to-Zygotic Transition (MZT), thousands of maternal transcripts are regulated, however, how different cis-elements and trans-factors are integrated to determine mRNA stability is still poorly understood. Here, we show that most transcripts are under combinatorial regulation by multiple decay pathways during zebrafish MZT. Using a massively parallel reporter assay, we identified cis-regulatory sequences in the 3’-UTR, including poly-U motifs that are associated with mRNA stability. In contrast, miR-430 target sequences, UAUUUAUU AU-rich elements (ARE), CCUC and CUGC elements emerged as destabilizing motifs, with miR-430 and AREs causing mRNA deadenylation upon genome activation. We identified trans-factors by profiling RNA-protein interactions and found that poly-U binding proteins are preferentially associated with 3’-UTR sequences and stabilizing motifs. We demonstrate that this activity is antagonized by poly-C motifs and correlated with protein binding. Finally, we integrated these regulatory motifs into a machine learning model that predicts reporter mRNA stability in vivo.This is the developmental mRNA-seq timecourse part of the study.