Genome wide analysis of 3'-UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish
Abstract
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 remains 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 U-rich motifs that are associated with increased 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 C-rich motifs and correlated with protein binding. Finally, we integrated these regulatory motifs into a machine learning model that predicts reporter mRNA stability in vivo.
- Received October 16, 2018.
- Accepted June 7, 2019.
- Published by Cold Spring Harbor Laboratory Press
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