Global analysis of binding sites of U2AF1 and ZRSR2 reveals RNA elements required for mutually exclusive splicing by the U2- and U12-type spliceosome.
Nucleic Acids Res
; 52(3): 1420-1434, 2024 Feb 09.
Article
em En
| MEDLINE
| ID: mdl-38088204
ABSTRACT
Recurring mutations in genes encoding 3' splice-site recognition proteins, U2AF1 and ZRSR2 are associated with human cancers. Here, we determined binding sites of the proteins to reveal that U2-type and U12-type splice sites are recognized by U2AF1 and ZRSR2, respectively. However, some sites are spliced by both the U2-type and U12-type spliceosomes, indicating that well-conserved consensus motifs in some U12-type introns could be recognized by the U2-type spliceosome. Nucleotides flanking splice sites of U12-type introns are different from those flanking U2-type introns. Remarkably, the AG dinucleotide at the positions -1 and -2 of 5' splice sites of U12-type introns with GT-AG termini is not present. AG next to 5' splice site introduced by a single nucleotide substitution at the -2 position could convert a U12-type splice site to a U2-type site. The class switch of introns by a single mutation and the bias against G at the -1 position of U12-type 5' splice site support the notion that the identities of nucleotides in exonic regions adjacent to splice sites are fine-tuned to avoid recognition by the U2-type spliceosome. These findings may shed light on the mechanism of selectivity in U12-type intron splicing and the mutations that affect splicing.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonucleoproteínas
/
Spliceossomos
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Sítios de Splice de RNA
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Fator de Processamento U2AF
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2024
Tipo de documento:
Article