2013年4月
FUS regulates genes coding for RNA-binding proteins in neurons by binding to their highly conserved introns.
RNA (New York, N.Y.)
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- 巻
- 19
- 号
- 4
- 開始ページ
- 498
- 終了ページ
- 509
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1261/rna.037804.112
Dominant mutations and mislocalization or aggregation of Fused in Sarcoma (FUS), an RNA-binding protein (RBP), cause neuronal degeneration in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD), two incurable neurological diseases. However, the function of FUS in neurons is not well understood. To uncover the impact of FUS in the neuronal transcriptome, we used high-throughput sequencing of immunoprecipitated and cross-linked RNA (HITS-CLIP) of FUS in human brains and mouse neurons differentiated from embryonic stem cells, coupled with RNA-seq and FUS knockdowns. We report conserved neuronal RNA targets and networks that are regulated by FUS. We find that FUS regulates splicing of genes coding for RBPs by binding to their highly conserved introns. Our findings have important implications for understanding the impact of FUS in neurodegenerative diseases and suggest that perturbations of FUS can impact the neuronal transcriptome via perturbations of RBP transcripts.
- リンク情報
- ID情報
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- DOI : 10.1261/rna.037804.112
- ISSN : 1355-8382
- PubMed ID : 23389473
- PubMed Central 記事ID : PMC3677260