Claudia Racca, Alejandra Gardiol, Taesun Eom, Jernej Ule, Antoine Triller, Robert B. Darnell
Abstract
Nova proteins are neuron-specific RNA binding proteins targeted by autoantibodies in a disorder manifest by failure of motor inhibition, and they regulate splicing and alternative 3' processing. Nova regulates splicing of RNAs encoding synaptic proteins, including the inhibitory glycine receptor alpha2 subunit (GlyRalpha2), and binds to others, including the GIRK2 channel. We found that Nova harbors functional NES and NLS elements, shuttles between the nucleus and cytoplasm, and that 50% of the protein localizes to the soma-dendritic compartment. Immunofluoresence and EM analysis of spinal cord motor neurons demonstrated that Nova co-localizes beneath synaptic contacts in dendrites with the same RNA, GlyRalpha2, whose splicing it regulates in the nucleus. HITS-CLIP identified intronic and 3' UTR sites where Nova binds to GlyRalpha2 and GIRK2 transcripts in the brain. This led directly to the identification of a 3' UTR localization element that mediates Nova-dependent localization of GIRK2 in primary neurons. These data demonstrate that HITS-CLIP can identify functional RNA localization elements, and they suggest new links between the regulation of nuclear RNA processing and mRNA localization.
Pharmacology, Toxicology and Pharmaceutical Science
2
2%
Other
3
3%
Unknown
15
15%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 September 2020.
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#13,358,992
of 22,660,862 outputs
Outputs from Frontiers in Neural Circuits
#579
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Outputs of similar age
#129,186
of 163,484 outputs
Outputs of similar age from Frontiers in Neural Circuits
#6
of 7 outputs
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