SERPING1 exon 3 splicing variants using alternative acceptor splice sites
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
30685616
DOI
10.1016/j.molimm.2019.01.007
PII: S0161-5890(18)30929-5
Knihovny.cz E-zdroje
- Klíčová slova
- Acceptor splice site, Alternative splicing, Exon 3, Hereditary angioedema, SERPING1,
- MeSH
- alternativní sestřih genetika MeSH
- buněčné jádro genetika MeSH
- buňky Hep G2 MeSH
- exony genetika MeSH
- inhibiční protein komplementu C1 genetika MeSH
- lidé MeSH
- malá interferující RNA metabolismus MeSH
- místa sestřihu RNA genetika MeSH
- mutace genetika MeSH
- nonsense mediated mRNA decay genetika MeSH
- sekvence nukleotidů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inhibiční protein komplementu C1 MeSH
- malá interferující RNA MeSH
- místa sestřihu RNA MeSH
- SERPING1 protein, human MeSH Prohlížeč
Mutations in the C1 inhibitor (C1INH) encoding gene, SERPING1, are associated with hereditary angioedema (HAE) which manifests as recurrent submucosal and subcutaneous edema episodes. The major C1INH function is the complement system inhibition, preventing its spontaneous activation. The presented study is focused on SERPING1 exon 3, an alternative and extraordinarily long exon (499 bp). Endogenous expression analysis performed in the HepG2, human liver, and human peripheral blood cells revealed several exon 3 splicing variants alongside exon inclusion: a highly prevalent exon skipping variant and less frequent +38 and -15 variants with alternative 3' splice sites (ss) located 38 and 15 nucleotides downstream and upstream from the authentic 3' ss, respectively. An exon skipping variant introducing a premature stop codon, represented nearly one third of all splicing variants and surprisingly appeared not to be degraded by NMD. The alternative -15 3' ss was used to a small extent, although predicted to be extremely weak. Its use was shown to be independent of its strength and highly sensitive to any changes in the surrounding sequence. -15 3' ss seems to be co-regulated with the authentic 3' ss, whose use is dependent mainly on its strength and less on the presence of intronic regulatory motifs. Subtle SERPING1 exon 3 splicing regulation can contribute to overall C1INH plasma levels and HAE pathogenesis.
Citace poskytuje Crossref.org
Deep Intronic Mutation in SERPING1 Caused Hereditary Angioedema Through Pseudoexon Activation
