The Critical Role of RNA m6A Methylation in Cancer

Cancer Research, Journal Year: 2019, Volume and Issue: 79(7), P. 1285 - 1292

Published: March 20, 2019

Since the identification of first RNA demethylase and establishment methylated immunoprecipitation-sequencing methodology 6 to 7 years ago, methylation has emerged as a widespread phenomenon critical regulator transcript expression. This new layer regulation is termed "epitranscriptomics." The most prevalent methylation, N6-methyladenosine (m6A), occurs in approximately 25% transcripts at genome-wide level enriched around stop codons, 5'- 3'-untranslated regions, within long internal exons. m6A modification regulates splicing, translocation, stability, translation into protein. catalyzed by methyltransferases METTL3, METTL14, METTL16 (writers), removed demethylases FTO ALKBH5 (erasers), interacts with m6A-binding proteins, such YTHDF1 IGF2BP1 (readers). methyltransferases, demethylases, proteins are frequently upregulated human cancer tissues from variety organ origins, increasing onco-transcript oncoprotein expression, cell proliferation, survival, tumor initiation, progression, metastasis. Although methyltransferase inhibitors not available yet, have shown promising anticancer effects vitro animal models cancer. Further screening for selective potent methyltransferase, demethylase, or protein may lead compounds suitable future clinical trials patients.

Language: Английский

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m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: June 25, 2019

Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N

Language: Английский

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RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(8), P. 4177 - 4338

Published: Jan. 3, 2018

With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, its functions are intimately linked to structure dynamics. Computer simulations, particular atomistic dynamics (MD), allow structural of biomolecular systems be investigated with unprecedented temporal spatial resolution. We here provide a comprehensive overview fast-developing field MD simulations RNA molecules. begin an in-depth, evaluatory coverage fundamental methodological challenges that set basis for future development field, particular, current developments inherent physical limitations force fields recent advances broad spectrum enhanced sampling methods. also survey closely related coarse-grained modeling systems. After dealing aspects, we exhaustive available simulation literature, ranging from studies smallest oligonucleotides investigations entire ribosome. Our review encompasses tetranucleotides, tetraloops, number small motifs, A-helix RNA, kissing-loop complexes, TAR element, decoding center other important regions ribosome, as well assorted others Extended sections devoted RNA–ion interactions, ribozymes, riboswitches, protein/RNA complexes. written audience possible, aiming much-needed interdisciplinary bridge between computation experiment, together perspective on field.

Language: Английский

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The epitranscriptome beyond m6A

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(2), P. 119 - 131

Published: Nov. 13, 2020

Language: Английский

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The RNA modification landscape in human disease

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

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