Splicing Enhancers at Intron–Exon Borders Participate in Acceptor Splice Sites Recognition

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209775%3A_____%2F20%3AN0000009" target="_blank" >RIV/00209775:_____/20:N0000009 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/1422-0067/21/18/6553" target="_blank" >https://www.mdpi.com/1422-0067/21/18/6553</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms21186553" target="_blank" >10.3390/ijms21186553</a>

Result language

angličtina

Original language name

Splicing Enhancers at Intron–Exon Borders Participate in Acceptor Splice Sites Recognition

Original language description

Acceptor splice site recognition (3´ splice site: 3´ ss) is a fundamental step in precursor messenger RNA (pre-mRNA) splicing. Generally, the U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor (U2AF) heterodimer recognizes the 3´ ss, of which U2AF35 has a dual function: (i) It binds to the intron–exon border of some 3´ ss and (ii) mediates enhancer-binding splicing activators’ interactions with the spliceosome. Alternative mechanisms for 3´ ss recognition have been suggested, yet they are still not thoroughly understood. Here, we analyzed 3´ ss recognition where the intron–exon border is bound by a ubiquitous splicing regulator SRSF1. Using the minigene analysis of two model exons and their mutants, BRCA2 exon 12 and VARS2 exon 17, we showed that the exon inclusion correlated much better with the predicted SRSF1 affinity than 3´ ss quality, which were assessed using the Catalog of Inferred Sequence Binding Preferences of RNA binding proteins (CISBP-RNA) database and maximum entropy algorithm (MaxEnt) predictor and the U2AF35 consensus matrix, respectively. RNA affinity purification proved SRSF1 binding to the model 3´ ss. On the other hand, knockdown experiments revealed that U2AF35 also plays a role in these exons’ inclusion. Most probably, both factors stochastically bind the 3´ ss, supporting exon recognition, more apparently in VARS2 exon 17. Identifying splicing activators as 3´ ss recognition factors is crucial for both a basic understanding of splicing regulation and human genetic diagnostics when assessing variants’ effects on splicing.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/NU20-02-00261" target="_blank" >NU20-02-00261: Mechanisms of the effect of genetic variants of LDL receptor and the role of genetic variants of lipoprotein(a) in the development of hypercholesterolemia in FH patients</a><br>

Continuities

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

Publication year

2020

Confidentiality

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

Name of the periodical

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Volume of the periodical

21

Issue of the periodical within the volume

18

Country of publishing house

CH - SWITZERLAND

Number of pages

18

Pages from-to

6553

UT code for WoS article

000581229300001

EID of the result in the Scopus database

2-s2.0-85090660569