The RNA modification landscape in human disease DOI Open Access

Nicky Jonkhout,

Julia Tran,

Martin A. Smith

et al.

RNA, Journal Year: 2017, Volume and Issue: 23(12), P. 1754 - 1769

Published: Aug. 30, 2017

RNA modifications have been historically considered as fine-tuning chemo-structural features of infrastructural RNAs, such rRNAs, tRNAs, and snoRNAs. This view has changed dramatically in recent years, to a large extent result systematic efforts map quantify various transcriptome-wide manner, revealing that are reversible, dynamically regulated, far more widespread than originally thought, involved major biological processes, including cell differentiation, sex determination, stress responses. Here we summarize the state knowledge provide catalog their links neurological disorders, cancers, other diseases. With advent direct RNA-sequencing technologies, expect this will help prioritize those for maps.

Language: Английский

Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation DOI
Huilin Huang, Hengyou Weng, Wenju Sun

et al.

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 20(3), P. 285 - 295

Published: Feb. 15, 2018

Language: Английский

Citations

2213

Reading, writing and erasing mRNA methylation DOI
Sara Zaccara, Ryan J. Ries, Samie R. Jaffrey

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(10), P. 608 - 624

Published: Sept. 13, 2019

Language: Английский

Citations

1906

The role of m6A modification in the biological functions and diseases DOI Creative Commons
Xiulin Jiang, Baiyang Liu, Zhi Nie

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Feb. 21, 2021

Abstract N 6 -methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher cells. m6A modified by methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, KIAA1429, and, removed demethylases, erasers, including FTO ALKBH5. It recognized m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 HNRNPA2B1, also known “readers”. Recent studies have shown that RNA plays essential role both physiological pathological conditions, initiation progression of different types human cancers. In this review, we discuss how methylation influences progressions hematopoietic, central nervous reproductive systems. We will mainly focus on recent progress identifying biological functions underlying molecular mechanisms methylation, its regulators downstream target genes, during cancer above propose process offer potential targets for therapy future.

Language: Английский

Citations

1400

Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism DOI Creative Commons
Ying Yang, Phillip J. Hsu, Yusheng Chen

et al.

Cell Research, Journal Year: 2018, Volume and Issue: 28(6), P. 616 - 624

Published: May 22, 2018

Abstract N 6 -methyladenosine (m A) is a chemical modification present in multiple RNA species, being most abundant mRNAs. Studies on enzymes or factors that catalyze, recognize, and remove m A have revealed its comprehensive roles almost every aspect of mRNA metabolism, as well variety physiological processes. This review describes the current understanding modification, particularly functions writers, erasers, readers with an emphasis role regulating isoform dosage

Language: Английский

Citations

1271

RNA N6‐methyladenosine methyltransferase‐like 3 promotes liver cancer progression through YTHDF2‐dependent posttranscriptional silencing of SOCS2 DOI Creative Commons

Mengnuo Chen,

Lai Wei, Cheuk‐Ting Law

et al.

Hepatology, Journal Year: 2017, Volume and Issue: 67(6), P. 2254 - 2270

Published: Nov. 24, 2017

Epigenetic alterations have contributed greatly to human carcinogenesis. Conventional epigenetic studies predominantly focused on DNA methylation, histone modifications, and chromatin remodeling. Recently, diverse reversible chemical modifications of RNAs emerged as a new layer regulation. N6‐methyladenosine (m6A) is the most abundant modification eukaryotic messenger RNA (mRNA) important for regulation mRNA stability, splicing, translation. Using transcriptome sequencing, we discovered that methyltransferase‐like 3 (METTL3), major N6‐adenosine methyltransferase, was significantly up‐regulated in hepatocellular carcinoma (HCC) multiple solid tumors. Clinically, overexpression METTL3 associated with poor prognosis patients HCC. Functionally, proved knockdown drastically reduced HCC cell proliferation, migration, colony formation vitro . Knockout remarkably suppressed tumorigenicity lung metastasis vivo On other hand, using CRISPR/dCas9‐VP64 activation system, demonstrated promoted growth both Through m6A methylated immuno‐precipitation quantitative reverse‐transcription polymerase chain reaction, identified suppressor cytokine signaling 2 (SOCS2) target METTL3‐mediated modification. Knockdown substantially abolished SOCS2 augmented expression. We also showed m6A‐mediated degradation relied reader protein YTHDF2‐dependent pathway. Conclusion : frequently contributes progression. represses expression through an m6A‐YTHDF2‐dependent mechanism. Our findings suggest mechanism alteration liver (H epatology 2018;67:2254‐2270).

Language: Английский

Citations

1116

G3BP1 Is a Tunable Switch that Triggers Phase Separation to Assemble Stress Granules DOI Creative Commons
Peiguo Yang, Cécile Mathieu, Regina‐Maria Kolaitis

et al.

Cell, Journal Year: 2020, Volume and Issue: 181(2), P. 325 - 345.e28

Published: April 1, 2020

Language: Английский

Citations

982

m6A Modification in Coding and Non-coding RNAs: Roles and Therapeutic Implications in Cancer DOI Creative Commons
Huilin Huang, Hengyou Weng, Jianjun Chen

et al.

Cancer Cell, Journal Year: 2020, Volume and Issue: 37(3), P. 270 - 288

Published: March 1, 2020

Language: Английский

Citations

935

Role of RNA modifications in cancer DOI
Isaia Barbieri, Tony Kouzarides

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(6), P. 303 - 322

Published: April 16, 2020

Language: Английский

Citations

928

The role of m6A RNA methylation in human cancer DOI Creative Commons
Xiaoyu Chen, Jing Zhang,

Jin‐Shui Zhu

et al.

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: May 29, 2019

N6-methyladenosine (m6A) is identified as the most common, abundant and conserved internal transcriptional modification, especially within eukaryotic messenger RNAs (mRNAs). M6A modification installed by m6A methyltransferases (METTL3/14, WTAP, RBM15/15B KIAA1429, termed "writers"), reverted demethylases (FTO ALKBH5, "erasers") recognized binding proteins (YTHDF1/2/3, IGF2BP1 HNRNPA2B1, "readers"). Acumulating evidence shows that, RNA methylation has an outsize effect on production/metabolism participates in pathogenesis of multiple diseases including cancers. Until now, molecular mechanisms underlying various tumors have not been comprehensively clarified. In this review, we mainly summarize recent advances biological function modifications human cancer discuss potential therapeutic strategies.

Language: Английский

Citations

852

Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis DOI Open Access
Phillip J. Hsu, Yunfei Zhu, Honghui Ma

et al.

Cell Research, Journal Year: 2017, Volume and Issue: 27(9), P. 1115 - 1127

Published: Aug. 15, 2017

Language: Английский

Citations

847