SERPING1 exon 3 splicing variants using alternative acceptor splice sites

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Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.
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GRYMOVÁ Tereza GRODECKÁ Lucie SOUČEK Přemysl FREIBERGER Tomáš

Rok publikování 2019
Druh Článek v odborném periodiku
Časopis / Zdroj Molecular Immunology
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www http://dx.doi.org/10.1016/j.molimm.2019.01.007
Doi http://dx.doi.org/10.1016/j.molimm.2019.01.007
Klíčová slova Alternative splicing; Acceptor splice site; SERPING1; Exon 3; Hereditary angioedema
Popis 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.
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