TY - JOUR TI - Regulatory consequences of neuronal ELAV-like protein binding to coding and non-coding RNAs in human brain AU - Scheckel, Claudia AU - Drapeau, Elodie AU - Frias, Maria A AU - Park, Christopher Y AU - Fak, John AU - Zucker-Scharff, Ilana AU - Kou, Yan AU - Haroutunian, Vahram AU - Ma'ayan, Avi AU - Buxbaum, Joseph D AU - Darnell, Robert B A2 - Black, Douglas L VL - 5 PY - 2016 DA - 2016/02/19 SP - e10421 C1 - eLife 2016;5:e10421 DO - 10.7554/eLife.10421 UR - https://doi.org/10.7554/eLife.10421 AB - Neuronal ELAV-like (nELAVL) RNA binding proteins have been linked to numerous neurological disorders. We performed crosslinking-immunoprecipitation and RNAseq on human brain, and identified nELAVL binding sites on 8681 transcripts. Using knockout mice and RNAi in human neuroblastoma cells, we showed that nELAVL intronic and 3' UTR binding regulates human RNA splicing and abundance. We validated hundreds of nELAVL targets among which were important neuronal and disease-associated transcripts, including Alzheimer's disease (AD) transcripts. We therefore investigated RNA regulation in AD brain, and observed differential splicing of 150 transcripts, which in some cases correlated with differential nELAVL binding. Unexpectedly, the most significant change of nELAVL binding was evident on non-coding Y RNAs. nELAVL/Y RNA complexes were specifically remodeled in AD and after acute UV stress in neuroblastoma cells. We propose that the increased nELAVL/Y RNA association during stress may lead to nELAVL sequestration, redistribution of nELAVL target binding, and altered neuronal RNA splicing. KW - alternative splicing KW - alzheimer's disease KW - nELAVL KW - mRNA stability KW - Y RNA KW - noncoding RNA KW - neuronal RNA binding protein JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -