ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism

The role of post-transcriptional gene regulation in human brain development and neurodevelopmental disorders remains mostly uncharacterized. ELAV-like RNA-binding proteins (RNAbps) are a family of proteins that regulate several aspects of neuronal function including neuronal excitability and synapti...

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Bibliographic Details
Published in:Human molecular genetics 2016-06, Vol.25 (12), p.2451-2464
Main Authors: Berto, Stefano, Usui, Noriyoshi, Konopka, Genevieve, Fogel, Brent L
Format: Article
Language:English
Subjects:
Autism Spectrum Disorder - genetics
Autism Spectrum Disorder - pathology
Brain - growth & development
Brain - metabolism
Brain - pathology
Cell Line
ELAV-Like Protein 2 - biosynthesis
ELAV-Like Protein 2 - genetics
Fragile X Mental Retardation Protein - genetics
Gene Expression Regulation, Developmental
Gene Regulatory Networks - genetics
High-Throughput Nucleotide Sequencing
Humans
Neurons - metabolism
Neurons - pathology
RNA Splicing - genetics
RNA Splicing Factors - genetics
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Summary:The role of post-transcriptional gene regulation in human brain development and neurodevelopmental disorders remains mostly uncharacterized. ELAV-like RNA-binding proteins (RNAbps) are a family of proteins that regulate several aspects of neuronal function including neuronal excitability and synaptic transmission, both critical to the normal function of the brain in cognition and behavior. Here, we identify the downstream neuronal transcriptional and splicing networks of ELAVL2, an RNAbp with previously unknown function in the brain. Expression of ELAVL2 was reduced in human neurons and RNA-sequencing was utilized to identify networks of differentially expressed and alternatively spliced genes resulting from haploinsufficient levels of ELAVL2. These networks contain a number of autism-relevant genes as well as previously identified targets of other important RNAbps implicated in autism spectrum disorder (ASD) including RBFOX1 and FMRP. ELAVL2-regulated co-expression networks are also enriched for neurodevelopmental and synaptic genes, and include genes with human-specific patterns of expression in the frontal pole. Together, these data suggest that ELAVL2 regulation of transcript expression is critical for neuronal function and clinically relevant to ASD.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/ddw110