Genome wide analysis of 3' UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish

Genome Res. 2019 Jul;29(7):1100-1114. doi: 10.1101/gr.245159.118. Epub 2019 Jun 21.


Posttranscriptional 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. By 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 show 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • Gene Expression Regulation, Developmental*
  • Machine Learning
  • Models, Genetic
  • RNA Stability / genetics*
  • RNA-Binding Proteins / metabolism*
  • Regulatory Sequences, Ribonucleic Acid
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zygote


  • 3' Untranslated Regions
  • RNA-Binding Proteins
  • Regulatory Sequences, Ribonucleic Acid