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

J 2020

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

KOVÁČOVÁ, Tatiana, Přemysl SOUČEK, Pavla HUJOVÁ, Tomáš FREIBERGER, Lucie GRODECKÁ et. al.

Základní údaje

Originální název

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

Autoři

KOVÁČOVÁ, Tatiana (703 Slovensko, domácí), Přemysl SOUČEK (203 Česká republika, domácí), Pavla HUJOVÁ (203 Česká republika, domácí), Tomáš FREIBERGER (203 Česká republika, domácí) a Lucie GRODECKÁ (203 Česká republika, garant)

Vydání

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2020, 1422-0067

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.923

Kód RIV

RIV/00216224:14110/20:00116880

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.3390/ijms21186553

UT WoS

000581229300001

Klíčová slova anglicky

pre-mRNA splicing; splicing enhancer; U2AF35; acceptor splice site recognition; SRSF1

Štítky

14110114, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 21. 7. 2021 10:28, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

MUNI/A/1099/2019, interní kód MU

Název: Faktory nespecifické imunity u některých imunopatologických stavů (Akronym: nespecif. imunita)

Investor: Masarykova univerzita, Faktory nespecifické imunity u některých imunopatologických stavů, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Citovat

KOVÁČOVÁ, Tatiana, Přemysl SOUČEK, Pavla HUJOVÁ, Tomáš FREIBERGER a Lucie GRODECKÁ. Splicing Enhancers at Intron-Exon Borders Participate in Acceptor Splice Sites Recognition. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2020, roč. 21, č. 18, s. 1-18. ISSN 1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms21186553.

@article{1690936,
   author = {Kováčová, Tatiana and Souček, Přemysl and Hujová, Pavla and Freiberger, Tomáš and Grodecká, Lucie},
   article_location = {Basel},
   article_number = {18},
   doi = {http://dx.doi.org/10.3390/ijms21186553},
   keywords = {pre-mRNA splicing; splicing enhancer; U2AF35; acceptor splice site recognition; SRSF1},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Splicing Enhancers at Intron-Exon Borders Participate in Acceptor Splice Sites Recognition},
   url = {https://www.mdpi.com/1422-0067/21/18/6553},
   volume = {21},
   year = {2020}
}

TY  - JOUR
ID  - 1690936
AU  - Kováčová, Tatiana - Souček, Přemysl - Hujová, Pavla - Freiberger, Tomáš - Grodecká, Lucie
PY  - 2020
TI  - Splicing Enhancers at Intron-Exon Borders Participate in Acceptor Splice Sites Recognition
JF  - International Journal of Molecular Sciences
VL  - 21
IS  - 18
SP  - 1-18
EP  - 1-18
PB  - Multidisciplinary Digital Publishing Institute
SN  - 14220067
KW  - pre-mRNA splicing
KW  - splicing enhancer
KW  - U2AF35
KW  - acceptor splice site recognition
KW  - SRSF1
UR  - https://www.mdpi.com/1422-0067/21/18/6553
L2  - https://www.mdpi.com/1422-0067/21/18/6553
N2  - 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.
ER  -

KOVÁČOVÁ, Tatiana, Přemysl SOUČEK, Pavla HUJOVÁ, Tomáš FREIBERGER a Lucie GRODECKÁ. Splicing Enhancers at Intron-Exon Borders Participate in Acceptor Splice Sites Recognition. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2020, roč.~21, č.~18, s.~1-18. ISSN~1422-0067. Dostupné z: https://dx.doi.org/10.3390/ijms21186553.

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