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Nat Commun ; 15(1): 3899, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724548

RESUMO

The epitranscriptome embodies many new and largely unexplored functions of RNA. A significant roadblock hindering progress in epitranscriptomics is the identification of more than one modification in individual transcript molecules. We address this with CHEUI (CH3 (methylation) Estimation Using Ionic current). CHEUI predicts N6-methyladenosine (m6A) and 5-methylcytosine (m5C) in individual molecules from the same sample, the stoichiometry at transcript reference sites, and differential methylation between any two conditions. CHEUI processes observed and expected nanopore direct RNA sequencing signals to achieve high single-molecule, transcript-site, and stoichiometry accuracies in multiple tests using synthetic RNA standards and cell line data. CHEUI's capability to identify two modification types in the same sample reveals a co-occurrence of m6A and m5C in individual mRNAs in cell line and tissue transcriptomes. CHEUI provides new avenues to discover and study the function of the epitranscriptome.


Assuntos
5-Metilcitosina , Adenosina , Análise de Sequência de RNA , Transcriptoma , Adenosina/análogos & derivados , Adenosina/metabolismo , 5-Metilcitosina/metabolismo , 5-Metilcitosina/análogos & derivados , Humanos , Metilação , Análise de Sequência de RNA/métodos , Processamento Pós-Transcricional do RNA , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , RNA/metabolismo , RNA/genética
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