The Renpenning syndrome-associated protein PQBP1 facilitates the nuclear import of splicing factor TXNL4A through the karyopherin ß2 receptor.
J Biol Chem
; 295(13): 4093-4100, 2020 03 27.
Article
em En
| MEDLINE
| ID: mdl-32041777
ABSTRACT
Renpenning syndrome belongs to a group of X-linked intellectual disability disorders. The Renpenning syndrome-associated protein PQBP1 (polyglutamine-binding protein 1) is intrinsically disordered, associates with several splicing factors, and is involved in pre-mRNA splicing. PQBP1 uses its C-terminal YxxPxxVL motif for binding to the splicing factor TXNL4A (thioredoxin like 4A), but the biological function of this interaction has yet to be elucidated. In this study, using recombinant protein expression, in vitro binding assays, and immunofluorescence microscopy in HeLa cells, we found that a recently reported X-linked intellectual disability-associated missense mutation, resulting in the PQBP1-P244L variant, disrupts the interaction with TXNL4A. We further show that this interaction is critical for the subcellular location of TXNL4A. In combination with other PQBP1 variants lacking a functional nuclear localization signal required for recognition by the nuclear import receptor karyopherin ß2, we demonstrate that PQBP1 facilitates the nuclear import of TXNL4A via a piggyback mechanism. These findings expand our understanding of the molecular basis of the PQBP1-TXNL4A interaction and of the etiology and pathogenesis of Renpenning syndrome and related disorders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paralisia Cerebral
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Ribonucleoproteína Nuclear Pequena U5
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Beta Carioferinas
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Deficiência Intelectual Ligada ao Cromossomo X
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Proteínas de Ligação a DNA
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China