Splicing Enhancers at Intron-Exon Borders Participate in Acceptor Splice Sites Recognition
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F20%3A00116880" target="_blank" >RIV/00216224:14110/20:00116880 - 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>
Alternative languages
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
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
—
Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
International Journal of Molecular Sciences
ISSN
1661-6596
e-ISSN
1422-0067
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
1-18
UT code for WoS article
000581229300001
EID of the result in the Scopus database
2-s2.0-85090660569