| Autor: |
Masaya, Hattori, Atsuko, Yabuuchi, Hayate, Tanaka, Taketo, Kawara, Hongyan, Wang, Koji, Inoue, Shunichi, Shiozawa, Koichiro, Komai |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Asian Pacific journal of allergy and immunology. |
| ISSN: |
0125-877X |
| Popis: |
Palindromic rheumatism (PR) is an infrequent form of periodic arthritis. Based on the similarity of the pathogenesis of PR to autoinflammatory syndromes, we previously found that the dominant-active splice variant of the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a CARD (ASC), which lacks exon 2 (Δexon2), is expressed in Japanese patients with PR.Elucidation of the mechanism of Δexon2 ASC production and the effect of IL-1β on splicing.The genomic DNA of Japanese patients with PR was sequenced. The effect of the observed single nucleotide polymorphisms (SNPs) on ASC splicing was determined via exon trapping using THP-1 cells stimulated with interleukin-1 beta (IL-1β) or ceramide. To investigate the genes that affect alternative splicing via IL-1β, we analyzed the transcriptome of IL-1β-treated THP-1 cells using RNA sequencing.We found the rs8056505 A-G SNP located in the 5'-untranslated region of the genomic ASC gene in patients and that Δexon2 expression was induced by this SNP, whereas it was suppressed by IL-1β or ceramide. We detected 131,426 transcripts and identified 52 differentially expressed genes (DEGs) consisting of 41 downregulated genes and 11 upregulated genes in IL-1β-stimulated THP-1 cells. The splicing-related gene MASCRNA was the most significantly induced gene by IL-1β.We propose a cyclic expression model in which ASC alternates between wild-type and Δexon2 expression regulated by the rs8056505 G allele and splicing factors induced by IL-1β. This cycle may be correlated with the formation of periodic PR pathologies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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