ID
45614
Description
Principal Investigator: Lionel B. Ivashkiv, MD, Hospital for Special Surgery, New York, NY, USA MeSH: Arthritis, Rheumatoid,Arthritis https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001371 During rheumatoid arthritis (RA), TNF activates fibroblast-like synoviocytes (FLS) inducing in a temporal order a constellation of genes, which perpetuate synovial inflammation. Although the molecular mechanisms regulating TNF-induced transcription are well characterized, little is known about the impact of mRNA stability on gene expression and the impact of TNF on decay rates of mRNA transcripts in FLS. To address these issues we performed RNA sequencing and genome-wide analysis of the mRNA stabilome in RA FLS. We found that TNF induces a biphasic gene expression program: initially, the inducible transcriptome consists primarily of unstable transcripts but progressively switches and becomes dominated by very stable transcripts. This temporal switch is due to: a) TNF-induced prolonged stabilization of previously unstable transcripts that enables progressive transcript accumulation over days and b) sustained expression and late induction of very stable transcripts. TNF- induced mRNA stabilization in RA FLS occurs during the late phase of TNF response, is MAPK-dependent, and involves several genes with pathogenic potential such as IL6, CXCL1, CXCL3, CXCL8/IL8, CCL2, and PTGS2. These results provide the first insights into genome-wide regulation of mRNA stability in RA FLS and highlight the potential contribution of dynamic regulation of the mRNA stabilome by TNF to chronic synovitis.
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- 2/25/23 2/25/23 - Simon Heim
Copyright Holder
Lionel B. Ivashkiv, MD, Hospital for Special Surgery, New York, NY, USA
Uploaded on
February 25, 2023
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License
Creative Commons BY 4.0
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dbGaP phs001371 Inflammation-Induced Stabilization of mRNA in Rheumatoid Arthritis
The subject consent data table contains subject IDs and consent group information.
- StudyEvent: SEV1
- The subject consent data table contains subject IDs and consent group information.
- This subject sample mapping data table includes a mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.
- This sample attributes data table includes body site where sample was collected, analyte type, TNF and ActD conditions.
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The subject consent data table contains subject IDs and consent group information.
- StudyEvent: SEV1
- The subject consent data table contains subject IDs and consent group information.
- This subject sample mapping data table includes a mapping of study subject IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample use.
- This sample attributes data table includes body site where sample was collected, analyte type, TNF and ActD conditions.
C2348585 (UMLS CUI [1,2])
C3846158 (UMLS CUI [1,2])