TY  - JOUR
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
Y1  - 2019/07/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1100 
EP  - 1114 
DO  - 10.1101/gr.245159.118 
VL  - 29 
IS  - 7 
UR  - http://genome.cshlp.org/content/29/7/1100.abstract 
N2  - 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. 
ER  -