SERPING1 exon 3 splicing variants using alternative acceptor
splice sites

J 2019

SERPING1 exon 3 splicing variants using alternative acceptor splice sites

GRYMOVÁ, Tereza, Lucie GRODECKÁ, Přemysl SOUČEK and Tomáš FREIBERGER

Basic information

Original name

SERPING1 exon 3 splicing variants using alternative acceptor splice sites

Authors

GRYMOVÁ, Tereza (203 Czech Republic), Lucie GRODECKÁ (203 Czech Republic), Přemysl SOUČEK (203 Czech Republic, guarantor, belonging to the institution) and Tomáš FREIBERGER (203 Czech Republic, belonging to the institution)

Edition

Molecular Immunology, OXFORD, PERGAMON-ELSEVIER SCIENCE LTD, 2019, 0161-5890

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.641

RIV identification code

RIV/00216224:14110/19:00108492

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.molimm.2019.01.007

UT WoS

000459951400012

Keywords in English

Alternative splicing; Acceptor splice site; SERPING1; Exon 3; Hereditary angioedema

Abstract

V originále

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.

Links

NV18-05-00330, research and development project

Name: Genetická determinace závažnosti otoků podmíněných bradykininem u pacientů s hereditárním angioedémem

Investor: Ministry of Health of the CR, Genetic determination of bradykinin-mediated angioedema severity in patients with hereditary angioedema

90043, large research infrastructures

Name: CIISB

Citovat

GRYMOVÁ, Tereza, Lucie GRODECKÁ, Přemysl SOUČEK and Tomáš FREIBERGER. SERPING1 exon 3 splicing variants using alternative acceptor splice sites. Molecular Immunology. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2019, vol. 107, MAR 2019, p. 91-96. ISSN 0161-5890. Available from: https://dx.doi.org/10.1016/j.molimm.2019.01.007.

@article{1545814,
   author = {Grymová, Tereza and Grodecká, Lucie and Souček, Přemysl and Freiberger, Tomáš},
   article_location = {OXFORD},
   article_number = {MAR 2019},
   doi = {http://dx.doi.org/10.1016/j.molimm.2019.01.007},
   keywords = {Alternative splicing; Acceptor splice site; SERPING1; Exon 3; Hereditary angioedema},
   language = {eng},
   issn = {0161-5890},
   journal = {Molecular Immunology},
   title = {SERPING1 exon 3 splicing variants using alternative acceptor splice sites},
   url = {http://dx.doi.org/10.1016/j.molimm.2019.01.007},
   volume = {107},
   year = {2019}
}

TY  - JOUR
ID  - 1545814
AU  - Grymová, Tereza - Grodecká, Lucie - Souček, Přemysl - Freiberger, Tomáš
PY  - 2019
TI  - SERPING1 exon 3 splicing variants using alternative acceptor splice sites
JF  - Molecular Immunology
VL  - 107
IS  - MAR 2019
SP  - 91-96
EP  - 91-96
PB  - PERGAMON-ELSEVIER SCIENCE LTD
SN  - 01615890
KW  - Alternative splicing
KW  - Acceptor splice site
KW  - SERPING1
KW  - Exon 3
KW  - Hereditary angioedema
UR  - http://dx.doi.org/10.1016/j.molimm.2019.01.007
L2  - http://dx.doi.org/10.1016/j.molimm.2019.01.007
N2  - 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.
ER  -

GRYMOVÁ, Tereza, Lucie GRODECKÁ, Přemysl SOUČEK and Tomáš FREIBERGER. SERPING1 exon 3 splicing variants using alternative acceptor splice sites. \textit{Molecular Immunology}. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2019, vol.~107, MAR 2019, p.~91-96. ISSN~0161-5890. Available from: https://dx.doi.org/10.1016/j.molimm.2019.01.007.

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