The RNA binding proteins TIA1 and TIAL1 protect germinal centre responses from apoptosis [iCLIP]
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ABSTRACT:
PROVIDER: PRJNA986857 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25010689.fastq.gz | Fastqsanger.gz | |||
| SRR25010690.fastq.gz | Fastqsanger.gz |
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Project description:Germinal centres (GC) are essential for the establishment of long-lasting antibody responses. In there, GC B cells rely on post-transcriptional RNA mechanisms for translating activation-associated transcriptional programs into functional changes in the cell proteome. However, we still lack knowledge about which are the critical proteins driving these key mechanisms. Here we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses. TIA1 and TIAL1- deficient GC B cells fail to undergo antigen-mediated positive selection, expansion and differentiation into B cell clones producing high-affinity antibodies. Mechanistically, TIA1 and TIAL1 control the transcriptional identity of dark and light zone GC B cells and enable timely expression of the pro-survival molecule MCL1. Altogether, we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells.
2023-08-29 | GSE235655 | GEO
Project description:Germinal centres (GC) are essential for the establishment of long-lasting antibody responses. In there, GC B cells rely on post-transcriptional RNA mechanisms for translating activation-associated transcriptional programs into functional changes in the cell proteome. However, we still lack knowledge about which are the critical proteins driving these key mechanisms. Here we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses. TIA1 and TIAL1- deficient GC B cells fail to undergo antigen- mediated positive selection, expansion and differentiation into B cell clones producing high-affinity antibodies. Mechanistically, TIA1 and TIAL1 control the transcriptional identity of dark and light zone GC B cells and enable timely expression of the pro-survival molecule MCL1. Altogether, we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells.
2023-08-29 | GSE235358 | GEO
Project description:The RNA binding proteins TIA1 and TIAL1 protect germinal centre responses from apoptosis
| PRJNA985742 | ENA
Project description:iCLIP and iCLAP for TIA1 and TIAL1 proteins
| PRJEB2628 | ENA
Project description:Individual nucleotide resolution UV-crosslinking and immunoprecipitation (iCLIP) and individual nucleotide resolution UV-crosslinking and affinity purification (iCLAP) were used to identify the global RNA binding sites for TIA1 and TIAL1 proteins. HeLa cells were UV crosslinked before lysing and digested with DNase and low concentration of RNase I. The protein-RNA complex were either immunoprecipitated with specific antibodies against either TIA1 or TIAL1 proteins and ligated to 3 prime adapter before separated by SDS-PAGE. For iCLAP, the His/Strep tagged proteins were overexpressed in HeLa cells, and the protein-RNA complexes were purified via Strep and His tag affinity purification. The proteins were digested by proteinase K and the RNA was reverse transcribed and self-circularised. The cDNA library was prepared by PCR with solexa primers compatible for high-throughput sequencing. This method allowed specific identify of crosslinked nucleotides, and genome-wide targets for TIA1 and TIAL1 not identified before. This method also allowed comparison between the 2 homologous proteins, whose binding sites and functions could be redundent. iCLAP provided an independent way to validate the binding sites identified by iCLIP, since no antibody was used in the iCLAP method.
2011-07-28 | E-MTAB-432 | biostudies-arrayexpress
Project description:B-cell lymphopoiesis requires dynamic modulation of the B-cell transcriptome at the post-transcriptional level, although the implication of RNA-binding proteins (RBPs) remain largely unknown. Here we show that the RBPs TIA1 and TIAL1 are essential in B cells and, if deleted, there is a developmental block at the pro-B cell stage. TIA1 and TIAL1 have redundant functions. They act together as global splicing regulators for the expression of mRNAs including those involved in DNA damage repair in pro-B cells. Mechanistically, TIA1 and TIAL1 bind to 5’splice sites for exon definition, splicing and expression of DNA damage sensors like Chek2 and Rif1. In their absence, pro-B cells show exacerbated DNA damage, altered P53 expression and increased cell death. Altogether, our study uncovers the importance of tight regulation of mRNA splicing by TIA1 and TIAL1 for the expression of integrative transcriptional programs for DNA damage sensing and repair during B-cell development.
2022-12-20 | GSE188556 | GEO
Project description:B-cell lymphopoiesis requires dynamic modulation of the B-cell transcriptome at the post-transcriptional level, although the implication of RNA binding proteins (RBPs) remain largely unknown. Here we show that the RBPs TIA1 and TIAL1 are essential in B cells and, if deleted, there is a developmental block at the pro-B cell stage. TIA1 and TIAL1 have redundant functions. They act together as global splicing regulators for the expression of mRNAs including those involved in DNA damage repair in pro-B cells. Mechanistically, TIA1 and TIAL1 bind to 5’splice sites for exon definition, splicing and expression of DNA damage sensors like Chek2 and Rif1. In their absence, pro-B cells show exacerbated DNA damage, altered P53 expression and increased cell death. Altogether, our study uncovers the importance of tight regulation of mRNA splicing by TIA1 and TIAL1 for the expression of integrative transcriptional programs for DNA damage sensing and repair during B-cell development.
2022-12-20 | GSE186701 | GEO
Project description:The purpose of this experiment was to characterize the network of proteins that interact with TIA1, and to investigate whether tau exerts control over TIA1 protein interactions, TIA1 was immunoprecipitated from cortical brain tissue of 10 month-old WT (C57BL/6J), tau-/- and TIA1-/- mice. The specificity of the TIA1 IP was verified by immunoblotting with anti-TIA1 antibody (Fig. 3A), and the resulting TIA1 proteome was examined by mass spectrometry.
2018-10-26 | PXD003922 | Pride
Project description:Germinal centers (GCs) are essential for the establishment of long-lasting antibody responses. GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome. However, the critical proteins driving these key mechanisms are still unknown. Here, we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses. TIA1- and TIAL1-deficient GC B cells fail to undergo antigen-mediated positive selection, expansion and differentiation into B-cell clones producing high-affinity antibodies. Mechanistically, TIA1 and TIAL1 control the transcriptional identity of dark- and light-zone GC B cells and enable timely expression of the prosurvival molecule MCL1. Thus, we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells.
| S-EPMC10469172 | biostudies-literature
Project description:During cell stress, the transcription and translation of immediate early genes are prioritized, while most other mRNAs are stored away in stress granules or degraded in P-bodies. TIA-1 is an mRNA binding protein that needs to translocate from the nucleus to seed the formation of stress granules in the cytoplasm. Since other stress granule components such as TDP-43, FUS, ATXN2, SMN, MAPT, HNRNPA2B1 and HNRNPA1 are crucial for the motor neuron diseases ALS / SMA and for the frontotemporal dementia FTD, here we studied mouse nervous tissue to identify mRNAs with selective dependence on Tia1 deletion. Transcriptome profiling with oligonucleotide microarrays in comparison of spinal cord and cerebellum, together with independent validation in quantitative reverse transcriptase PCR and immunoblots demonstrated several strong and consistent dysregulations. In agreement with previously reported TIA1 knock-down effects, cell cycle and apoptosis regulators were affected markedly with expression changes up to 2-fold, exhibiting increased levels for Cdkn1a, Ccnf, and Tprkb versus decreased levels for Bid and Inca1 transcripts. Novel and surprisingly strong expression alterations were detected for fat storage and membrane trafficking factors, with prominent above 3-fold upregulations of Plin4, Wdfy1, Tbc1d24, and Pnpla2, versus a 0.5 -fold?? downregulation of Cntn4 transcript, encoding an axonal membrane adhesion factor with established haploinsufficiency. In comparison subtle effects on the RNA processing machinery included up to 1.2-fold upregulations of Dcp1b and Tial1. The effect on lipid dynamics factors is noteworthy, since also the gene deletion of Tardbp (encoding TDP-43) and Atxn2 led to fat metabolism phenotypes in mouse. In conclusion, genetic ablation of the stress granule nucleator TIA-1 has a novel major effect on mRNAs encoding lipid homeostasis factors in the brain. Factorial design comparing Tia1 knock-out mice with wild type littermates in four different tissues (midbrain, cerebellum, liver, spinal cord) and 2 different ages.
2014-10-06 | E-GEOD-54418 | biostudies-arrayexpress