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Cited by 308RNA modifications and cancerEpigenetics and DNA MethylationRNA regulation and disease

Crosstalk between epitranscriptomic and epigenetic mechanisms in gene regulation

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Kan, Ryan L., Chen, Jianjun, Sallam, Tamer·2022·Trends in Genetics
DOI 10.1016/j.tig.2021.06.014PMC PMC9093201
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Abstract

Epigenetic modifications occur on genomic DNA and histones to influence gene expression. More recently, the discovery that mRNA undergoes similar chemical modifications that powerfully impact transcript turnover and translation adds another layer of dynamic gene regulation. Central to precise and synchronized regulation of gene expression is intricate crosstalk between multiple checkpoints involved in transcript biosynthesis and processing. There are more than 100 internal modifications of RNA in mammalian cells. The most common is N 6 -methyladenosine (m 6 A) methylation. Although m 6 A is established to influence RNA stability dynamics and translation efficiency, rapidly accumulating evidence shows significant crosstalk between RNA methylation and histone/DNA epigenetic mechanisms. These interactions specify transcriptional outputs, translation, recruitment of chromatin modifiers, as well as the deployment of the m 6 A methyltransferase complex (MTC) at target sites. In this review, we dissect m 6 A-orchestrated feedback circuits that regulate histone modifications and the activity of regulatory RNAs, such as long noncoding (lnc)RNA and chromosome-associated regulatory RNA. Collectively, this body of evidence suggests that m 6 A acts as a versatile checkpoint that can couple different layers of gene regulation with one another.

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Authors
Kan, R. L., Chen, J., & Sallam, T.
Affiliations
  • University of California, Los Angeles (US)
  • City Of Hope National Medical Center (US)
Corresponding author
Sallam, Tamer
ORCID
Venue
Trends in Genetics
Publisher
Elsevier BV
Published
2022-02
Volume
38
Issue
2
Pages
182-193
ISSN
0168-9525 (ISSN-L)
DOI
10.1016/j.tig.2021.06.014
PMC
PMC9093201
OpenAlex
W3183307215
Cited by
308
References
63
Citations by year
2026: 59 · 2025: 89 · 2024: 59 · 2023: 55 · 2022: 39 · 2021: 6 · 2012: 1
FWCI
4.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Trends in Genetics (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Funders
  • Burroughs Wellcome Fund (HL139549, HL149766, CA214965, CA236399, CA243386, DK118086)
  • American Heart Association (HL139549, HL149766, CA214965, CA236399, CA243386, DK118086)
  • Leukemia and Lymphoma Society (HL139549, HL149766, CA214965, CA236399, CA243386, DK118086)
  • National Heart, Lung, and Blood Institute (HL139549, HL149766, CA214965, CA236399, CA243386, DK118086)
  • National Cancer Institute (HL139549, HL149766, CA214965, CA236399, CA243386, DK118086)
  • National Institute of Diabetes and Digestive and Kidney Diseases (HL139549, HL149766, CA214965, CA236399, CA243386, DK118086)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
N6-methyladenosine, RNA methylation, epitranscriptomics, epigenetics, histone modifications, gene expression regulation, long non-coding RNA, m6A methyltransferase complex, RNA stability, translation efficiency, chromatin modifiers, transcript processing
MeSH terms
Animals, Gene Expression Regulation, Histones, Methylation, DNA Methylation, Epigenesis, Genetic, RNA, Long Noncoding

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