m(6)A-LAIC-seq reveals the census and complexity of the m(6)A epitranscriptome.
Nat Methods
; 13(8): 692-8, 2016 08.
Article
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| MEDLINE
| ID: mdl-27376769
ABSTRACT
N(6)-Methyladenosine (m(6)A) is a widespread, reversible chemical modification of RNA molecules, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m(6)A modified ('m(6)A levels') or the relationship of m(6)A modification(s) to alternative RNA isoforms. To deconvolute the m(6)A epitranscriptome, we developed m(6)A-level and isoform-characterization sequencing (m(6)A-LAIC-seq). We found that cells exhibit a broad range of nonstoichiometric m(6)A levels with cell-type specificity. At the level of isoform characterization, we discovered widespread differences in the use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3' untranslated regions, while nonmethylated transcript isoforms tend to use distal APA sites. m(6)A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m(6)A modifications.
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1
Banco de datos:
MEDLINE
Asunto principal:
Adenosina
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Regulación de la Expresión Génica
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Epigénesis Genética
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Secuenciación de Nucleótidos de Alto Rendimiento
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Epigenómica
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Transcriptoma
Límite:
Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article