Abstract
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.
Highlights
RNA binding proteins (RBPs) associate with RNAs throughout their life cycle, regulating all aspects of RNA metabolism and function
Tissue samples were derived from BA9, which is part of the dorsolateral prefrontal cortex (Figure 1A), a brain area that is damaged in later stages of Alzheimer’s disease (AD) and that is important for executive functions such as working memory, cognitive flexibility, planning, inhibition, and abstract reasoning (O’Reilly, 2010)
We purified Neuronal ELAV-like (nELAVL)-RNP complexes with antiserum reactive to all three nELAVL proteins (Figure 1B). 32P-labeled nELAVL-RNP complexes were not recovered with control serum or in the absence of UV-irradiation (Figure 1B)
Summary
RNA binding proteins (RBPs) associate with RNAs throughout their life cycle, regulating all aspects of RNA metabolism and function. Biochemistry Neuroscience eLife digest When a gene is active, its DNA is copied into a molecule of RNA. This molecule undergoes a process called splicing which removes certain segments, and the resulting ‘messenger RNA’ molecule is translated into protein. Many messenger RNAs go through alternative splicing, whereby different segments can be included or excluded from the final molecule. This allows more than one type of protein to be produced from a single gene
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
