title: FUS regulates genes coding for RNA-binding proteins in neurons by binding to their highly conserved introns.
abstract: 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.
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Tadashi
authors: T
authors: Nakaya
authors: Panagiotis
authors: P
authors: Alexiou
authors: Manolis
authors: M
authors: Maragkakis
authors: Alexandra
authors: A
authors: Chang
authors: Zissimos
authors: Z
authors: Mourelatos
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007438:Introns; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics*; D013702:Temporal Lobe / Q000378:metabolism
chemical_list: D016601:RNA-Binding Proteins
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