In:
Genome Research, Cold Spring Harbor Laboratory, Vol. 29, No. 7 ( 2019-07), p. 1100-1114
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′ 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.
Type of Medium:
Online Resource
ISSN:
1088-9051
,
1549-5469
DOI:
10.1101/gr.245159.118
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2019
detail.hit.zdb_id:
1483456-X
SSG:
12
