RUNX1/RUNX1T1 mediates alternative splicing and reorganises the transcriptional landscape in leukemia.
Nat Commun
; 12(1): 520, 2021 01 22.
Article
em En
| MEDLINE
| ID: mdl-33483506
ABSTRACT
The fusion oncogene RUNX1/RUNX1T1 encodes an aberrant transcription factor, which plays a key role in the initiation and maintenance of acute myeloid leukemia. Here we show that the RUNX1/RUNX1T1 oncogene is a regulator of alternative RNA splicing in leukemic cells. The comprehensive analysis of RUNX1/RUNX1T1-associated splicing events identifies two principal mechanisms that underlie the differential production of RNA isoforms (i) RUNX1/RUNX1T1-mediated regulation of alternative transcription start site selection, and (ii) direct or indirect control of the expression of genes encoding splicing factors. The first mechanism leads to the expression of RNA isoforms with alternative structure of the 5'-UTR regions. The second mechanism generates alternative transcripts with new junctions between internal cassettes and constitutive exons. We also show that RUNX1/RUNX1T1-mediated differential splicing affects several functional groups of genes and produces proteins with unique conserved domain structures. In summary, this study reveals alternative splicing as an important component of transcriptome re-organization in leukemia by an aberrant transcriptional regulator.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide
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Regulação Leucêmica da Expressão Gênica
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Proteínas de Fusão Oncogênica
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Processamento Alternativo
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Subunidade alfa 2 de Fator de Ligação ao Core
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Proteína 1 Parceira de Translocação de RUNX1
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article