Post-transcriptional 3´-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments

Yuval Malka (), Avital Steiman-Shimony, Eran Rosenthal, Liron Argaman, Leonor Cohen-Daniel, Eliran Arbib, Hanah Margalit, Tommy Kaplan () and Michael Berger ()
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Yuval Malka: The Hebrew University
Avital Steiman-Shimony: The Hebrew University
Eran Rosenthal: The Hebrew University
Liron Argaman: The Hebrew University
Leonor Cohen-Daniel: The Hebrew University
Eliran Arbib: The Hebrew University
Hanah Margalit: The Hebrew University
Tommy Kaplan: The Hebrew University
Michael Berger: The Hebrew University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract The majority of mammalian genes contain one or more alternative polyadenylation sites. Choice of polyadenylation sites was suggested as one of the underlying mechanisms for generating longer/shorter transcript isoforms. Here, we demonstrate that mature mRNA transcripts can undergo additional cleavage and polyadenylation at a proximal internal site in the 3′-UTR, resulting in two stable, autonomous, RNA fragments: a coding sequence with a shorter 3′-UTR (body) and an uncapped 3′-UTR sequence downstream of the cleavage point (tail). Analyses of the human transcriptome has revealed thousands of such cleavage positions, suggesting a widespread post-transcriptional phenomenon producing thousands of stable 3′-UTR RNA tails that exist alongside their transcripts of origin. By analyzing the impact of microRNAs, we observed a significantly stronger effect for microRNA regulation at the body compared to the tail fragments. Our findings open a variety of future research prospects and call for a new perspective on 3′-UTR-dependent gene regulation.

Date: 2017
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DOI: 10.1038/s41467-017-02099-7

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