Identification of a new exon 2-skipped TNFR1 transcript: regulation by three functional polymorphisms of the TNFR-associated periodic syndrome (TRAPS) gene

Rittore, Cécile; Sanchez, Elodie; Soler, Stephan; Barat‐Houari, Mouna; Albers, Marieke; Obici, Laura; McDermott, Michael F.; Touitou, Isabelle; Grandemange, Sylvie

doi:10.1136/annrheumdis-2012-203023

Cited by 12 publications

(20 citation statements)

References 37 publications

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“…Point mutations/variations are also known to cause alternative splicing. Rittore et al (2014) showed three variations [rs4149570(c.-610G > T), rs767455(c.36A > G,pPro12Pro), rs1800692(c.473-33C > T)] in the promoter, exon 1 and intron 2, respectively, of TNFRSF1A gene enhance the splicing of exon 2 in vitro . These variations appeared to have a role in the pathogenesis of TRAPS disease ( Rittore et al , 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“… Rittore et al (2014) showed three variations [rs4149570(c.-610G > T), rs767455(c.36A > G,pPro12Pro), rs1800692(c.473-33C > T)] in the promoter, exon 1 and intron 2, respectively, of TNFRSF1A gene enhance the splicing of exon 2 in vitro . These variations appeared to have a role in the pathogenesis of TRAPS disease ( Rittore et al , 2014 ). Furthermore, in another study, Tone et al (2011) suggested that c.910G > A variant (rs75977701) leads to the skipping of MEFV exon 2.…”

Section: Discussionmentioning

confidence: 99%

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Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models

et al. 2017

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The function of gene body DNA methylation in alternative splicing, and its relation to disease pathogenesis is not fully elucidated. The gene for familial Mediterranean fever (MEFV) encodes the pyrin protein and contains a 998 bp CpG island, covering the second exon, which is differentially methylated in FMF patients compared to healthy controls. Our further observation of increased exon 2-spliced MEFV transcript in leukocytes of FMF patients provoked us to test the role of exon methylation in alternative splicing using inflammatory cell culture models. First, in vitro exon methylation triggered an increased level of exon 2 exclusion using a splicing cassette in a promyelocytic leukemia cell line (HL-60). HL-60 cells subjected to methylating and demethylating agents, as well as cells differentiated to neutrophil-like cells, exhibited different levels of spliced/unspliced transcripts. We observed increased levels of spliced transcripts in neutrophil-like (p = 0.0005), activated (p = 0.0034) and methylated cells (p < 0.0001), whereas decreased levels in demethylated cells (p = 0.0126) compared to control untreated HL-60 cells. We also showed that the protein isoform of pyrin lacking the exon 2 has an adverse subcellular localization in neutrophil-like cells. Therefore, it remains in the cytoplasm rather than the nucleus. This may point to an epigenetic involvement in an important inflammatory gene.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models

et al. 2017

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“…Another detailed study described a TNFR1 transcript lacking exon 2 (TNFR1-d2) and its association with a specific haplotype at 3 single nucleotide polymorphisms (SNPs) previously associated with TNF-receptor-associated periodic syndrome (TRAPS). These SNPs have distant locations along the TNFR1A gene: rs4149570 lies at the promoter region (c.610G>T), rs767455 at exon 1 (c.36A>G) and rs1800692 at exon 4 (c.473-33C>T), so it is plausible that an interplay of transcription and splicing dynamics determines transcript outcome ( 16 ). This evidence strongly suggests that these SNPs disrupt splicing enhancers/silencers along intronic or exonic sequences, an aspect yet to be studied for other reported SNPs associated with TRAPS ( 17 ) or other inflammatory conditions, including Crohn's disease ( 18 ).…”

Section: Known Isoforms In Tnf Signalingmentioning

confidence: 99%

“…The demonstration by Rittore et al ( 16 ) that SNPs can have an effect on the alternative splicing pattern of the TNFR1 gene may be the cornerstone that joins two groups of association studies, namely, transcript diversity and SNPs, and sheds light on their association. The Rittore group identified that SNPs rs4149570, rs767455 and rs1800692 have a combined effect on the TNFR1 transcript output through regulation of alternative splicing.…”

Section: Splicing Potentialmentioning

confidence: 99%

Alternative splicing regulation in tumor necrosis factor‑mediated inflammation (Review)

2017

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It is generally accepted that alternative splicing has an effect on disease when it leads to conspicuous changes in relevant proteins, but that the combinatorial effect of several small modifications can have marked outcomes as well. Inflammation is a complex process involving numerous signaling pathways, among which the tumor necrosis factor (TNF) pathway is one of the most studied. Signaling pathways are commonly represented as intricate cascades of molecular interactions that eventually lead to the activation of one or several genes. Alternative splicing is a common means of controlling protein expression in time and space; therefore, it can modulate the outcome of signaling pathways through small changes in their elements. Notably, the overall process is tightly regulated, which is easily overlooked when analyzing the pathway as a whole. The present review summarizes recent studies of the alternative splicing of key players of the TNF pathway leading to inflammation, and hypothesizes on the cumulative results of those modifications and the impact on cancer development.

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“…[ 7 8 ] Some authors have also utilized the ultrasonography to predict the outcome after local steroid injection. [ 9 10 ] It has been demonstrated that the therapeutic success of local steroid injection is mainly associated with the finding of power Doppler signal. [ 9 ] The initial median nerve swelling and its ratio have also been presented as a predictor of response after steroid injection.…”

Section: Introductionmentioning

confidence: 99%

Ultrasonography Predictive Factors of Response to Local Steroid Injection in Patients with Carpal Tunnel Syndrome

et al. 2018

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Background:The aim of this study is to determine the predictive value of ultrasonography for results of local steroid injection in patients with carpal tunnel syndrome (CTS).Materials and Methods:This prospective cohort study was conducted during a 1-year period in outpatient clinics of rehabilitation and physical medicine including 35 patients with moderate and severe CTS who receive ultrasonography-guided local steroid injection. The Boston self-assessment questionnaire and electrodiagnosis parameters were recorded at baseline, 1 month, and 3 months after therapy. We also recorded the baseline ultrasonography parameters to determine the predictors of outcome.Results:The sensory severity score and functional status scale along with electrodiagnosis parameters decreased significantly at 1 month (P < 0.001) and remained unchanged after 3 months. Volar bulging was negatively associated with sensory nerve action potential latency (r = −0.392; P = 0.020). Cross-sectional area (CSA) of maximal swelling (MS; r = 0.409; P = 0.015), CSA at 2-cm of MS (r = 0.563; P < 0.001), and CSA at 12-cm of MS (r = 0.521; P = 0.001) correlated positively with compound muscle action potential (CMAP) amplitude while maximal swelling/12-cm MS ratio (r = −0.439; P = 0.008) and maximal swelling/2-cm MS ratio (r = −0.342; P = 0.045) correlated negatively. CSA at 12-cm of MS also correlated positively with CMAP amplitude nerve conduction velocity (r = 0.436; P = 0.010).Conclusion:Volar bulging, CSA of maximal swelling, CSA of MS at 2-cm, and CSA of MS at 12-cm are among the ultrasonographic predictors of response to local steroid injection in patients with CTS.

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Identification of a new exon 2-skipped TNFR1 transcript: regulation by three functional polymorphisms of the TNFR-associated periodic syndrome (TRAPS) gene

Cited by 12 publications

References 37 publications

Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models

Alternatively spliced MEFV transcript lacking exon 2 and its protein isoform pyrin-2d implies an epigenetic regulation of the gene in inflammatory cell culture models

Alternative splicing regulation in tumor necrosis factor‑mediated inflammation (Review)

Ultrasonography Predictive Factors of Response to Local Steroid Injection in Patients with Carpal Tunnel Syndrome

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