title: Identification of in vivo, conserved, TAF15 RNA binding sites reveals the impact of TAF15 on the neuronal transcriptome.
abstract: RNA binding proteins (RBPs) have emerged as major causative agents of amyotrophic lateral sclerosis (ALS). To investigate the function of TAF15, an RBP recently implicated in ALS, we explored its target RNA repertoire in normal human brain and mouse neurons. Coupling high-throughput sequencing of immunoprecipitated and crosslinked RNA with RNA sequencing and TAF15 knockdowns, we identified conserved TAF15 RNA targets and assessed the impact of TAF15 on the neuronal transcriptome. We describe a role of TAF15 in the regulation of splicing for a set of neuronal RNAs encoding proteins with essential roles in synaptic activities. We find that TAF15 is required for a critical alternative splicing event of the zeta-1 subunit of the glutamate N-methyl-D-aspartate receptor (Grin1) that controls the activity and trafficking of NR1. Our study uncovers neuronal RNA networks impacted by TAF15 and sets the stage for investigating the role of TAF15 in ALS pathogenesis.
authors: Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Fadia
authors: F
authors: Ibrahim
authors: Manolis
authors: M
authors: Maragkakis
authors: Panagiotis
authors: P
authors: Alexiou
authors: Margaret A
authors: MA
authors: Maronski
authors: Marc A
authors: MA
authors: Dichter
authors: Zissimos
authors: Z
authors: Mourelatos
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C409466:NR1 NMDA receptor; D034741:RNA, Small Interfering; D016194:Receptors, N-Methyl-D-Aspartate; D035381:TATA-Binding Protein Associated Factors; D012313:RNA