The splicing regulators TIA1 and TIAL1 are required for the expression of the DNA damage repair machinery during B cell lymphopoiesis

B cell lymphopoiesis requires dynamic modulation of the B cell transcriptome for timely coordination of somatic mutagenesis and DNA repair in progenitor B (pro-B) cells. Here, we show that, in pro-B cells, the RNA-binding proteins T cell intracellular antigen 1 (TIA1) and TIA1-like protein (TIAL1) a...

Full description

Saved in:
Bibliographic Details
Published in:Cell reports (Cambridge) 2022-12, Vol.41 (12), p.111869, Article 111869
Main Authors: Osma-Garcia, Ines C., Capitan-Sobrino, Dunja, Mouysset, Mailys, Aubert, Yann, Maloudi, Orlane, Turner, Martin, Diaz-Muñoz, Manuel D.
Format: Article
Language:English
Subjects:
apoptosis
B cell development
Biochemistry, Molecular Biology
Development Biology
DNA Damage
DNA damage repair
DNA Repair
Genomics
immunoglobulin VDJ recombination
Life Sciences
Lymphopoiesis - genetics
Poly(A)-Binding Proteins - metabolism
post-transcriptional gene regulation
pro-B cells
progenitor B cells
RNA Splice Sites
RNA Splicing
T-Cell Intracellular Antigen-1 - genetics
T-Cell Intracellular Antigen-1 - metabolism
TIA1
TIAL1
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:B cell lymphopoiesis requires dynamic modulation of the B cell transcriptome for timely coordination of somatic mutagenesis and DNA repair in progenitor B (pro-B) cells. Here, we show that, in pro-B cells, the RNA-binding proteins T cell intracellular antigen 1 (TIA1) and TIA1-like protein (TIAL1) act redundantly to enable developmental progression. They are global splicing regulators that control the expression of hundreds of mRNAs, including those involved in DNA damage repair. Mechanistically, TIA1 and TIAL1 bind to 5′ splice sites for exon definition, splicing, and expression of DNA damage sensors, such as Chek2 and Rif1. In their absence, pro-B cells show exacerbated DNA damage, altered P53 expression, and increased cell death. Our study uncovers the importance of tight regulation of RNA splicing by TIA1 and TIAL1 for the expression of integrative transcriptional programs that control DNA damage sensing and repair during B cell development. [Display omitted] •Post-transcriptional regulation by TIA1 and TIAL1 is needed for B cell development•VDJ recombination is impaired in the absence of TIA1 and TIAL1•TIA1 and TIAL1 control exon definition and splicing in progenitor B cells•TIA1 and TIAL1 are required for the expression of DNA damage repair machinery Tight control of VDJ recombination, cell selection, and cell proliferation is required for the development of an ample B cell repertoire. Osma-Garcia et al. report the need of TIA1/TIAL1-dependent post-transcriptional regulation for splicing and expression of key DNA damage sensors and repair proteins that enable BCR formation and B cell generation.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2022.111869