Science advances · 2024
Huntingtin is an RNA binding protein and participates in NEAT1-mediated paraspeckles.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Yadav Manisha, Harding Rachel J, Li Tiantian, Xu Xin, Gall-Duncan Terence, Khan Mahreen, Bardile Costanza Ferrari, Sequiera Glen L, Duan Shili, Chandrasekaran Renu, Pan Anni, Bu Jiachuan, Yamazaki Tomohiro, Hirose Tetsuro, Prinos Panagiotis, Tippett Lynette, Turner Clinton, Curtis Maurice A, Faull Richard L M, Pouladi Mahmoud A, Pearson Christopher E, He Housheng Hansen, Arrowsmith Cheryl H
Аннотация
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.