Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1.
Genome Biol
; 22(1): 171, 2021 06 03.
Article
em En
| MEDLINE
| ID: mdl-34082786
ABSTRACT
BACKGROUND:
Somatic cell reprogramming is the process that allows differentiated cells to revert to a pluripotent state. In contrast to the extensively studied rewiring of epigenetic and transcriptional programs required for reprogramming, the dynamics of post-transcriptional changes and their associated regulatory mechanisms remain poorly understood. Here we study the dynamics of alternative splicing changes occurring during efficient reprogramming of mouse B cells into induced pluripotent stem (iPS) cells and compare them to those occurring during reprogramming of mouse embryonic fibroblasts.RESULTS:
We observe a significant overlap between alternative splicing changes detected in the two reprogramming systems, which are generally uncoupled from changes in transcriptional levels. Correlation between gene expression of potential regulators and specific clusters of alternative splicing changes enables the identification and subsequent validation of CPSF3 and hnRNP UL1 as facilitators, and TIA1 as repressor of mouse embryonic fibroblasts reprogramming. We further find that these RNA-binding proteins control partially overlapping programs of splicing regulation, involving genes relevant for developmental and morphogenetic processes.CONCLUSIONS:
Our results reveal common programs of splicing regulation during reprogramming of different cell types and identify three novel regulators of this process and their targets.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Processamento Alternativo
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Fator de Especificidade de Clivagem e Poliadenilação
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Ribonucleoproteínas Nucleares Heterogêneas
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Reprogramação Celular
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Antígeno-1 Intracelular de Células T
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article