A Massively Parallel Reporter Assay of 3' UTR Sequences Identifies In Vivo Rules for mRNA Degradation

Rabani, Michal and Pieper, Lindsey and Chew, Guo-Liang and Schier, Alexander F.. (2017) A Massively Parallel Reporter Assay of 3' UTR Sequences Identifies In Vivo Rules for mRNA Degradation. Molecular Cell, 68 (6). pp. 1083-1094.e5.

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Official URL: https://edoc.unibas.ch/73220/

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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 in vivo 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell and Developmental Biology (Schier)
UniBasel Contributors:Schier, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Mar 2020 13:47
Deposited On:31 Mar 2020 13:47

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