SERPING1 exon 3 splicing variants using alternative acceptor splice sites

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209775%3A_____%2F19%3AN0000012" target="_blank" >RIV/00209775:_____/19:N0000012 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/19:00108492

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0161589018309295" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0161589018309295</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molimm.2019.01.007" target="_blank" >10.1016/j.molimm.2019.01.007</a>

Jazyk výsledku

angličtina

Název v původním jazyce

SERPING1 exon 3 splicing variants using alternative acceptor splice sites

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

SERPING1 exon 3 splicing variants using alternative acceptor splice sites

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Immunology

ISSN

0161-5890

e-ISSN

—

Svazek periodika

107

Číslo periodika v rámci svazku

January 2019

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

91-96

Kód UT WoS článku

000459951400012

EID výsledku v databázi Scopus

2-s2.0-85060334154