NOVA1 explained

RNA-binding protein Nova-1 is a protein that in humans is encoded by the NOVA1 gene.^{[1] [2]}

This gene encodes a neuron-specific RNA-binding protein, a member of the Nova family of paraneoplastic disease antigens, that is recognized and inhibited by paraneoplastic antibodies. These antibodies are found in the sera of patients with paraneoplastic opsoclonus-ataxia, breast cancer, and small cell lung cancer. Alternatively spliced transcripts encoding distinct isoforms have been described. Both Neanderthals and Denisovans had one version and nearly all modern humans had another suggesting positive selection. Insertion of Neanderthal gene variant of the neuro-oncological ventral antigen 1 (NOVA1) gene into human cortical organoids might promote slower development and higher surface complexity in the brain models,^[3] but this may be an artefact of a CRISPR side effect,^{[4] [5]} as it could not be replicated in a subsequent study.^[6]

Further reading

• Buckanovich RJ, Posner JB, Darnell RB . Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system . Neuron . 11 . 4 . 657–72 . 1993 . 8398153 . 10.1016/0896-6273(93)90077-5 . 22554933 .
• Buckanovich RJ, Darnell RB . The neuronal RNA binding protein Nova-1 recognizes specific RNA targets in vitro and in vivo . Mol. Cell. Biol. . 17 . 6 . 3194–201 . 1997 . 10.1128/MCB.17.6.3194 . 9154818 . 232172 .
• Lewis HA, Chen H, Edo C, etal . Crystal structures of Nova-1 and Nova-2 K-homology RNA-binding domains . Structure . 7 . 2 . 191–203 . 1999 . 10368286 . 10.1016/S0969-2126(99)80025-2 . free .
• Jensen KB, Dredge BK, Stefani G, etal . Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability . Neuron . 25 . 2 . 359–71 . 2000 . 10719891 . 10.1016/S0896-6273(00)80900-9 . free .
• Dias Neto E, Correa RG, Verjovski-Almeida S, etal . Shotgun sequencing of the human transcriptome with ORF expressed sequence tags . Proc. Natl. Acad. Sci. U.S.A. . 97 . 7 . 3491–6 . 2000 . 10737800 . 10.1073/pnas.97.7.3491 . 16267 . 2000PNAS...97.3491D . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Dredge BK, Darnell RB . Nova regulates GABA(A) receptor gamma2 alternative splicing via a distal downstream UCAU-rich intronic splicing enhancer . Mol. Cell. Biol. . 23 . 13 . 4687–700 . 2003 . 12808107 . 10.1128/MCB.23.13.4687-4700.2003 . 164843 .
• Brandenberger R, Wei H, Zhang S, etal . Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation . Nat. Biotechnol. . 22 . 6 . 707–16 . 2005 . 15146197 . 10.1038/nbt971 . 27764390 .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Ule J, Ule A, Spencer J, etal . Nova regulates brain-specific splicing to shape the synapse . Nat. Genet. . 37 . 8 . 844–52 . 2005 . 16041372 . 10.1038/ng1610 . 8446567 .
• Lim J, Hao T, Shaw C, etal . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–14 . 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . free .

Notes and References

1. Buckanovich RJ, Yang YY, Darnell RB . The onconeural antigen Nova-1 is a neuron-specific RNA-binding protein, the activity of which is inhibited by paraneoplastic antibodies . J Neurosci . 16 . 3 . 1114–22 . Feb 1996 . 10.1523/JNEUROSCI.16-03-01114.1996 . 8558240 . 6578795 .
2. Web site: Entrez Gene: NOVA1 neuro-oncological ventral antigen 1.
3. Web site: Neanderthal Gene Variant Alters Neurodevelopment in Human Brain Organoids. 11 February 2021.
4. Maricic . Tomislav . Helmbrecht . Nelly . Riesenberg . Stephan . Macak . Dominik . Kanis . Philipp . Lackner . Martin . Pugach-Matveeva . Agrafena Daria . Pääbo . Svante . 2021-10-15 . Comment on "Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment" . Science . en . 374 . 6565 . eabi6060 . 10.1126/science.abi6060 . 34648345 . 238990790 . 0036-8075.
5. Herai . Roberto H. . Szeto . Ryan A. . Trujillo . Cleber A. . Muotri . Alysson R. . 2021-10-15 . Response to Comment on "Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment" . Science . en . 374 . 6565 . eabi9881 . 10.1126/science.abi9881 . 34648331 . 238990560 . 0036-8075.
6. Riesenberg . Stephan . Kanis . Philipp . Macak . Dominik . Wollny . Damian . Düsterhöft . Dorothee . Kowalewski . Johannes . Helmbrecht . Nelly . Maricic . Tomislav . Pääbo . Svante . 2023-07-20 . Efficient high-precision homology-directed repair-dependent genome editing by HDRobust . Nature Methods . 20 . 9 . 1388–1399 . en . 10.1038/s41592-023-01949-1 . 1548-7091. free . 37474806 . 10482697 .