RT Journal
A1 Vejnar, Charles E.
A1 Abdel Messih, Mario
A1 Takacs, Carter M.
A1 Yartseva, Valeria
A1 Oikonomou, Panos
A1 Christiano, Romain
A1 Stoeckius, Marlon
A1 Lau, Stephanie
A1 Lee, Miler T.
A1 Beaudoin, Jean-Denis
A1 Musaev, Damir
A1 Darwich-Codore, 
Hiba
A1 Walther, Tobias C.
A1 Tavazoie, Saeed
A1 Cifuentes, Daniel
A1 Giraldez, Antonio J.
T1 Genome wide analysis of 3′ UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish
JF Genome Research 
JO Genome Research 
YR 2019 
FD July 01 
VO 29 
IS 7 
SP 1100 
OP 1114 
DO 10.1101/gr.245159.118 
UL http://genome.cshlp.org/content/29/7/1100.abstract 
AB 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.