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Journal ArticleDOI

Epitranscriptome sequencing technologies: decoding RNA modifications

Xiaoyu Li, +2 more
- 01 Jan 2017 - 
- Vol. 14, Iss: 1, pp 23-31
TLDR
This Review focuses on the major mRNA modifications in the transcriptome of eukaryotic cells: N6-methyladenosine, N6, 2′-O-dimethyladenosines, 5-methylcytidine, 5.hydroxylmethylcyTidine, inosine, pseudouridine and N1-methyl adenosine.
Abstract
In recent years, major breakthroughs in RNA-modification-mediated regulation of gene expression have been made, leading to the emerging field of epitranscriptomics.Our understanding of the distribution, regulation and function of these dynamic RNA modifications is based on sequencing technologies. In this Review, we focus on the major mRNA modifications in the transcriptome of eukaryotic cells: N6-methyladenosine, N6, 2'-O-dimethyladenosine, 5-methylcytidine, 5-hydroxylmethylcytidine, inosine, pseudouridine and N1-methyladenosine. We discuss the sequencing technologies used to profile these epitranscriptomic marks, including scale, resolution, quantitative feature, pre-enrichment capability and the corresponding bioinformatics tools. We also discuss the challenges of epitranscriptome profiling and highlight the prospect of future detection tools. We aim to guide the choice of different detection methods and inspire new ideas in RNA biology.

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Citations
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Journal ArticleDOI

Temporal Control of Mammalian Cortical Neurogenesis by m6A Methylation

TL;DR: It is shown that m6A depletion by Mettl14 knockout in embryonic mouse brains prolongs the cell cycle of radial glia cells and extends cortical neurogenesis into postnatal stages and uncovers previously unappreciated transcriptional prepatterning in cortical neural stem cells.
Journal ArticleDOI

The role of m6A modification in the biological functions and diseases.

TL;DR: In this paper, the authors discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems.
Journal ArticleDOI

The RNA modification landscape in human disease.

TL;DR: This work summarizes the state of knowledge and provides a catalog of RNA modifications and their links to neurological disorders, cancers, and other diseases, expecting that this catalog will help prioritize those RNA modifications for transcriptome-wide maps.
References
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Journal ArticleDOI

Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1

TL;DR: It is shown here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro.
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Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons

TL;DR: A method is presented for transcriptome-wide m(6)A localization, which combines m( 6)A-specific methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-Seq) and reveals insights into the epigenetic regulation of the mammalian transcriptome.
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N6-methyladenosine-dependent regulation of messenger RNA stability

TL;DR: It is shown that m6A is selectively recognized by the human YTH domain family 2 (YTHDF2) ‘reader’ protein to regulate mRNA degradation and established the role of YTH DF2 in RNA metabolism, showing that binding of Y THDF2 results in the localization of bound mRNA from the translatable pool to mRNA decay sites, such as processing bodies.
Journal ArticleDOI

N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.

TL;DR: FTO exhibits efficient oxidative demethylation activity of abundant N6-methyladenosine (m6A) residues in RNA in vitro, and it is shown that FTO partially colocalizes with nuclear speckles, supporting m6A in nuclear RNA as a physiological substrate of FTO.
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