PUBLICATION
Genome wide analysis of 3'-UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish
- Authors
- Vejnar, C.E., Abdelmessih, M., Takacs, C., Yartseva, V., Oikonomou, P., Christiano, R., Stoeckius, M., Lau, S., Lee, M., Beaudoin, J.D., Musaev, D., Darwich-Codore, H., Walther, T., Tavazoie, S., Cifuentes, D., Giraldez, A.
- ID
- ZDB-PUB-190624-2
- Date
- 2019
- Source
- Genome research 29(7): 1100-1114 (Journal)
- Registered Authors
- Cifuentes, Daniel, Giraldez, Antonio, Lee, Miler, Takacs, Carter M., Vejnar, Charles
- Keywords
- none
- 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
- PubMed
- 31227602 Full text @ Genome Res.
Citation
Vejnar, C.E., Abdelmessih, M., Takacs, C., Yartseva, V., Oikonomou, P., Christiano, R., Stoeckius, M., Lau, S., Lee, M., Beaudoin, J.D., Musaev, D., Darwich-Codore, H., Walther, T., Tavazoie, S., Cifuentes, D., Giraldez, A. (2019) Genome wide analysis of 3'-UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish. Genome research. 29(7):1100-1114.
Abstract
Post-transcriptional 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. 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 demonstrate 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping