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, Michael Berger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageAmerican English
Article number2029
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2017

Bibliographical note

Funding Information:
We thank M. Bronstein for helping with the construction of the RNA libraries for sequencing, Y. Nevo for helping with the data analysis, S. Sarfati for assisting with graphics, T. Ben-Zvi for technical assistance and N. Friedman for comments on the manuscript. This work was supported by grants from the Israel Science Foundation (grant nos.1275/12 and 913/15), the Israel Cancer Research Fund (grant no. 13/726/ RCDA), Marie Curie People (grant no. 322006), and the Concern Foundation. T.K. and E.R. were supported by a Marie Curie CIG grant no. 618327. A.S.-S., E.R., H.M., and T.K. are members of the Israeli Center of Excellence (I-CORE) for Gene Regulation in Complex Human Disease (no. 41/11) and the Israeli Center of Excellence (I-CORE) for Chromatin and RNA in Gene Regulation (no. 1796/12).

Publisher Copyright:
© 2017, The Author(s).


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