A Massively Parallel Reporter Assay of 3' UTR Sequences Identifies InáVivo Rules for mRNA Degradation
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4519600
Author(s) Rabani, Michal; Pieper, Lindsey; Chew, Guo-Liang; Schier, Alexander F.
Author(s) at UniBasel Schier, Alexander
Year 2017
Title A Massively Parallel Reporter Assay of 3' UTR Sequences Identifies InáVivo Rules for mRNA Degradation
Journal Molecular Cell
Volume 68
Number 6
Pages / Article-Number 1083-+
Keywords 3′; RNA degradation; RNA stability regulation; UTR; massively parallel reporter assay; maternal to zygotic transition
Mesh terms 3' Untranslated Regions; Animals; Embryo, Nonmammalian, cytology, metabolism; Gene Expression Regulation; Genes, Reporter; MicroRNAs; RNA Stability; RNA, Messenger; Zebrafish, genetics, growth & development, metabolism; Zebrafish Proteins, metabolism; Zygote, growth & development, metabolism
Abstract The stability of mRNAs is regulated by signals within their sequences, but a systematic and predictive understanding of the underlying sequence rules remains elusive. Here we introduce UTR-seq, a combination of massively parallel reporter assays and regression models, to survey the dynamics of tens of thousands of 3' UTR sequences during early zebrafish embryogenesis. UTR-seq revealed two temporal degradation programs: a maternally encoded early-onset program and a late-onset program that accelerated degradation after zygotic genome activation. Three signals regulated early-onset rates: stabilizing poly-U and UUAG sequences and destabilizing GC-rich signals. Three signals explained late-onset degradation: miR-430 seeds, AU-rich sequences, and Pumilio recognition sites. Sequence-based regression models translated 3' UTRs into their unique decay patterns and predicted the inávivo effect of sequence signals on mRNA stability. Their application led to the successful design of artificial 3' UTRs that conferred specific mRNA dynamics. UTR-seq provides a general strategy to uncover the rules of RNA cis regulation.
Publisher CELL PRESS
ISSN/ISBN 1097-4164
URL https://www.sciencedirect.com/science/article/pii/S1097276517308730?via%3Dihub
edoc-URL https://edoc.unibas.ch/73220/
Full Text on edoc No
Digital Object Identifier DOI 10.1016/j.molcel.2017.11.014
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/29225039
ISI-Number WOS:000418607500007
Document type (ISI) Article
 
   

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11/08/2020