Huntingtin is an RNA binding protein and participates in NEAT1-mediated paraspeckles.
Sci Adv
; 10(29): eado5264, 2024 Jul 19.
Article
de En
| MEDLINE
| ID: mdl-39028820
ABSTRACT
Huntingtin protein, mutated in Huntington's disease, is implicated in nucleic acid-mediated processes, yet the evidence for direct huntingtin-nucleic acid interaction is limited. Here, we show wild-type and mutant huntingtin copurify with nucleic acids, primarily RNA, and interact directly with G-rich RNAs in in vitro assays. Huntingtin RNA-immunoprecipitation sequencing from patient-derived fibroblasts and neuronal progenitor cells expressing wild-type and mutant huntingtin revealed long noncoding RNA NEAT1 as a significantly enriched transcript. Altered NEAT1 levels were evident in Huntington's disease cells and postmortem brain tissues, and huntingtin knockdown decreased NEAT1 levels. Huntingtin colocalized with NEAT1 in paraspeckles, and we identified a high-affinity RNA motif preferred by huntingtin. This study highlights NEAT1 as a huntingtin interactor, demonstrating huntingtin's involvement in RNA-mediated functions and paraspeckle regulation.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéines de liaison à l'ARN
/
Maladie de Huntington
/
ARN long non codant
/
Protéine huntingtine
Limites:
Humans
Langue:
En
Journal:
Sci Adv
/
Sci. Adv
/
Science advances
Année:
2024
Type de document:
Article
Pays d'affiliation:
Canada
Pays de publication:
États-Unis d'Amérique