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

doi:10.1038/s41467-017-02099-7

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 journal › Article › peer-review

39 Scopus citations

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.

Original language	English
Article number	2029
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-02099-7
State	Published - 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).

Access to Document

10.1038/s41467-017-02099-7

Cite this

@article{914e9490bd7d434bb2add3dc5b197d9a,

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

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.",

author = "Yuval Malka and Avital Steiman-Shimony and Eran Rosenthal and Liron Argaman and Leonor Cohen-Daniel and Eliran Arbib and Hanah Margalit and Tommy Kaplan and Michael Berger",

note = "Publisher Copyright: {\textcopyright} 2017, The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41467-017-02099-7",

language = "אנגלית",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - Post-transcriptional 3´-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments

AU - Malka, Yuval

AU - Steiman-Shimony, Avital

AU - Rosenthal, Eran

AU - Argaman, Liron

AU - Cohen-Daniel, Leonor

AU - Arbib, Eliran

AU - Margalit, Hanah

AU - Kaplan, Tommy

AU - Berger, Michael

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85054842325&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-02099-7

DO - 10.1038/s41467-017-02099-7

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 29229900

AN - SCOPUS:85054842325

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2029

ER -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this