Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
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 the...
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doaj-928f71eebddd447f9050eb912dcd59922021-06-06T11:51:10ZengBMCGenome Biology1474-760X2021-06-0122113010.1186/s13059-021-02372-5Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1Claudia Vivori0Panagiotis Papasaikas1Ralph Stadhouders2Bruno Di Stefano3Anna Ribó Rubio4Clara Berenguer Balaguer5Serena Generoso6Anna Mallol7José Luis Sardina8Bernhard Payer9Thomas Graf10Juan Valcárcel11Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyAbstract 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.https://doi.org/10.1186/s13059-021-02372-5Alternative splicingSomatic cell reprogrammingCPSF3hnRNP UL1TIA1Pluripotency |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Claudia Vivori Panagiotis Papasaikas Ralph Stadhouders Bruno Di Stefano Anna Ribó Rubio Clara Berenguer Balaguer Serena Generoso Anna Mallol José Luis Sardina Bernhard Payer Thomas Graf Juan Valcárcel |
spellingShingle |
Claudia Vivori Panagiotis Papasaikas Ralph Stadhouders Bruno Di Stefano Anna Ribó Rubio Clara Berenguer Balaguer Serena Generoso Anna Mallol José Luis Sardina Bernhard Payer Thomas Graf Juan Valcárcel Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1 Genome Biology Alternative splicing Somatic cell reprogramming CPSF3 hnRNP UL1 TIA1 Pluripotency |
author_facet |
Claudia Vivori Panagiotis Papasaikas Ralph Stadhouders Bruno Di Stefano Anna Ribó Rubio Clara Berenguer Balaguer Serena Generoso Anna Mallol José Luis Sardina Bernhard Payer Thomas Graf Juan Valcárcel |
author_sort |
Claudia Vivori |
title |
Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1 |
title_short |
Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1 |
title_full |
Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1 |
title_fullStr |
Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1 |
title_full_unstemmed |
Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1 |
title_sort |
dynamics of alternative splicing during somatic cell reprogramming reveals functions for rna-binding proteins cpsf3, hnrnp ul1, and tia1 |
publisher |
BMC |
series |
Genome Biology |
issn |
1474-760X |
publishDate |
2021-06-01 |
description |
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. |
topic |
Alternative splicing Somatic cell reprogramming CPSF3 hnRNP UL1 TIA1 Pluripotency |
url |
https://doi.org/10.1186/s13059-021-02372-5 |
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