生物
免疫沉淀
RNA结合蛋白
非翻译区
RNA剪接
核糖核酸
信使核糖核酸
基因
三素数非翻译区
报告基因
基因表达
细胞生物学
基因表达调控
选择性拼接
心理压抑
遗传学
作者
Michael A. Rieger,Dana King,Haley Crosby,Yating Liu,Barak A. Cohen,Joseph D. Dougherty
出处
期刊:Cell Reports
[Elsevier]
日期:2020-12-01
卷期号:33 (12): 108531-108531
被引量:15
标识
DOI:10.1016/j.celrep.2020.108531
摘要
CELF6 is a CELF-RNA-binding protein, and thus part of a protein family with roles in human disease; however, its mRNA targets in the brain are largely unknown. Using cross-linking immunoprecipitation and sequencing (CLIP-seq), we define its CNS targets, which are enriched for 3' UTRs in synaptic protein-coding genes. Using a massively parallel reporter assay framework, we test the consequence of CELF6 expression on target sequences, with and without mutating putative binding motifs. Where CELF6 exerts an effect on sequences, it is largely to decrease RNA abundance, which is reversed by mutating UGU-rich motifs. This is also the case for CELF3-5, with a protein-dependent effect on magnitude. Finally, we demonstrate that targets are derepressed in CELF6-mutant mice, and at least two key CNS proteins, FOS and FGF13, show altered protein expression levels and localization. Our works find, in addition to previously identified roles in splicing, that CELF6 is associated with repression of its CNS targets via the 3' UTR in vivo.
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