Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

In eukaryotes, almost all RNA species are processed at their 3′ ends and most mRNAs are polyadenylated in the nucleus by canonical poly(A) polymerases. In recent years, several terminal nucleotidyl transferases (TENTs) including non-canonical poly(A) polymerases (ncPAPs) and terminal uridyl transferases (TUTases) have been discovered. In contrast to canonical polymerases, TENTs' functions are more diverse; some, especially TUTases, induce RNA decay while others, such as cytoplasmic ncPAPs, activate translationally dormant deadenylated mRNAs. The mammalian genome encodes 11 different TENTs. This review summarizes the current knowledge about the functions and mechanisms of action of these enzymes.

This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.

Related collections

Most cited references 186

Record: found
Abstract: found
Article: not found

Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.

Inha Heo, Chirlmin Joo, Jun Soo Cho … (2008)

The precise control of microRNA (miRNA) biogenesis is critical for embryonic development and normal cellular functions, and its dysregulation is often associated with human diseases. Though the birth and maturation pathway of miRNA has been established, the regulation and death pathway remains largely unknown. Here, we report the RNA-binding proteins, Lin28a and Lin28b, as posttranscriptional repressors of let-7 miRNA biogenesis. We observe that the Lin28 proteins act mainly in the cytoplasm by inducing uridylation of precursor let-7 (pre-let-7) at its 3' end. The uridylated pre-let-7 (up-let-7) fails Dicer processing and undergoes degradation. We provide a mechanism for the posttranscriptional regulation of miRNA biogenesis by Lin28 which is highly expressed in undifferentiated cells and certain cancer cells. The Lin28-mediated downregulation of let-7 may play a key role in development, stem cell programming, and tumorigenesis.

0 comments Cited 333 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

L1 retrotransposition in human neural progenitor cells.

Nicole Coufal, Jose L. Garcia-Perez, Grace Peng … (2009)

Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo. Here we demonstrate that neural progenitor cells isolated from human fetal brain and derived from human embryonic stem cells support the retrotransposition of engineered human L1s in vitro. Furthermore, we developed a quantitative multiplex polymerase chain reaction that detected an increase in the copy number of endogenous L1s in the hippocampus, and in several regions of adult human brains, when compared to the copy number of endogenous L1s in heart or liver genomic DNAs from the same donor. These data suggest that de novo L1 retrotransposition events may occur in the human brain and, in principle, have the potential to contribute to individual somatic mosaicism.

0 comments Cited 316 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation.

Inha Heo, Chirlmin Joo, Young-Kook Kim … (2009)

As key regulators in cellular functions, microRNAs (miRNAs) themselves need to be tightly controlled. Lin28, a pluripotency factor, was reported to downregulate let-7 miRNA by inducing uridylation of let-7 precursor (pre-let-7). But the enzyme responsible for the uridylation remained unknown. Here we identify a noncanonical poly (A) polymerase, TUTase4 (TUT4), as the uridylyl transferase for pre-let-7. Lin28 recruits TUT4 to pre-let-7 by recognizing a tetra-nucleotide sequence motif (GGAG) in the terminal loop. TUT4 in turn adds an oligouridine tail to the pre-let-7, which blocks Dicer processing. Other miRNAs with the same sequence motif (miR-107, -143, and -200c) are regulated through the same mechanism. Knockdown of TUT4 and Lin28 reduces the level of stem cell markers, suggesting that they are required for stem cell maintenance. This study uncovers the role of TUT4 and Lin28 as specific suppressors of miRNA biogenesis, which has implications for stem cell research and cancer biology.

0 comments Cited 292 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Philos Trans R Soc Lond B Biol Sci

Journal ID (iso-abbrev): Philos. Trans. R. Soc. Lond., B, Biol. Sci

Journal ID (publisher-id): RSTB

Journal ID (hwp): royptb

Title: Philosophical Transactions of the Royal Society B: Biological Sciences

Publisher: The Royal Society

ISSN (Print): 0962-8436

ISSN (Electronic): 1471-2970

Publication date (Print): 19 December 2018

Publication date (Electronic): 5 November 2018

Publication date PMC-release: 5 November 2018

Volume: 373

Issue: 1762 , Theme issue ‘5′ and 3′ modifications controlling RNA degradation’ organized and edited by Dominique Gagliardi and Andrzej Dziembowski

Electronic Location Identifier: 20180162

Affiliations

[1 ]Department of RNA Metabolism, Institute of Bioorganic Chemistry, Polish Academy of Sciences , Noskowskiego 12/14, Poznan, Poland

[2 ]Laboratory of RNA Biology and Functional Genomics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences , Pawinskiego 5a, 02-106 Warsaw, Poland

[3 ]Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw , Pawinskiego 5a, 02-106 Warsaw, Poland

Author notes

e-mail: zwarkocki@ 123456ibch.poznan.pl

e-mail: andrzejd@ 123456ibb.waw.pl

One contribution of 11 to a theme issue ‘ 5′ and 3′ modifications controlling RNA degradation’.

Author information

Zbigniew Warkocki http://orcid.org/0000-0002-1684-1635

Andrzej Dziembowski http://orcid.org/0000-0001-8492-7572

Article

Publisher ID: rstb20180162

DOI: 10.1098/rstb.2018.0162

PMC ID: 6232586

PubMed ID: 30397099

SO-VID: 831e0572-e24f-4975-bd2d-db086fd1a144

License:

Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

History

Date accepted : 1 October 2018

Funding

Funded by: European Research Council;

Award ID: 309419

Funded by: Foundation for Polish Science;

Award ID: TEAM/2016-1/3

Funded by: Narodowe Centrum Nauki, http://dx.doi.org/10.13039/501100004281;

Award ID: 2017/26/D/NZ1/00887

Custom metadata

cover-date December 19, 2018

ScienceOpen disciplines: Philosophy of science

Keywords: tent,non-canonical polyadenylation,rna uridylation,tutase,rna stability,rna metabolism

Data availability:

ScienceOpen disciplines: Philosophy of science

Keywords: tent, non-canonical polyadenylation, rna uridylation, tutase, rna stability, rna metabolism

Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism

Read this article at

Abstract

Related collections

RNA drug delivery

Most cited references 186

Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.

L1 retrotransposition in human neural progenitor cells.

TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 316

Cited by 26

Most referenced authors 2,555