NOVA1
Description
The NOVA1 (NOVA alternative splicing regulator 1) is a protein-coding gene located on chromosome 14.
NOVA1 is a neuron-specific RNA-binding protein encoded by the NOVA1 gene in humans. It is a member of the Nova family of paraneoplastic disease antigens, which are recognized and inhibited by antibodies found in patients with certain cancers. These antibodies can be found in the sera of patients with paraneoplastic opsoclonus-ataxia, breast cancer, and small cell lung cancer. NOVA1 has distinct isoforms that result from alternative splicing. Interestingly, Neanderthals and Denisovans had one version of the NOVA1 gene, while nearly all modern humans have another version, suggesting positive selection during human evolution. A study investigating the effect of inserting the Neanderthal version of NOVA1 into human cortical organoids showed potential for slower development and higher surface complexity in the brain models. However, this finding might be an artefact due to a CRISPR side effect, as it could not be replicated in a subsequent study.
NOVA1 is a neuron-specific RNA-binding protein that regulates alternative splicing by binding to specific sequences (5'-YCAY-3') within pre-mRNA. This binding can either activate or repress exon inclusion, depending on the location of the binding site. When NOVA1 binds to an exonic 5'-YCAY-3' cluster, it blocks U1 snRNP binding and exon inclusion. Conversely, binding to an intronic 5'-YCAY-3' cluster enhances spliceosome assembly and exon inclusion. NOVA1 also autoregulates its own expression by acting as a splicing repressor. It activates the inclusion of specific exons in other genes, such as exon E3A in the glycine receptor alpha-2 chain and exon E9 in the gamma-aminobutyric-acid receptor gamma-2 subunit. NOVA1 is involved in regulating a novel glycine receptor alpha-2 chain splice variant (alpha-2N) in developing spinal cord. It interacts directly with PTBP2.
NOVA1 is also known as Nova-1.
