%0 Journal Article
%T Genome wide analysis of 3¡ä UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish
%A Antonio J. Giraldez
%A Carter M. Takacs
%A Charles E. Vejnar
%A Damir Musaev
%A Daniel Cifuentes
%A Hiba Darwich-Codore
%A Jean-Denis Beaudoin
%A Mario Abdel Messih
%A Marlon Stoeckius
%A Miler T. Lee
%A Panos Oikonomou
%A Romain Christiano
%A Saeed Tavazoie
%A Stephanie Lau
%A Tobias C. Walther
%A Valeria Yartseva
%J Genome Research
%D 2019
%R Jean-Denis Beaudoin http://www.genome.org/cgi/doi/10.1101/gr.245159.118
%X Abstract 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¡ä 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¨Cprotein interactions and found that poly(U)-binding proteins are preferentially associated with 3¡ä 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
%U https://genome.cshlp.org/content/29/7/1100.abstract