Sequence-specific RNA binding by a Nova KH domain: Implications for paraneoplastic disease and the fragile X syndrome

Hal A. Lewis, Kiran Musunuru, Kirk B. Jensen, Carme Edo, Hua Chen, Robert B. Darnell, Stephen K. Burley

Research output: Contribution to journalArticle

250 Scopus citations

Abstract

The structure of a Nova protein K homology (KH) domain recognizing single-stranded RNA has been determined at 2.4 Å resolution. Mammalian Nova antigens (1 and 2) constitute an important family of regulators of RNA metabolism in neurons, first identified using sera from cancer patients with the autoimmune disorder paraneoplastic opsoclonus-myoclonus ataxia (POMA). The structure of the third KH domain (KH3) of Nova-2 bound to a stem loop RNA resembles a molecular vise, with 5'-Ura-Cyt-Ade-Cyt-3' pinioned between an invariant Gly-X-X-Gly motif and the variable loop. Tetranucleotide recognition is supported by an aliphatic α helix/β sheet RNA-binding platform, which mimics 5'-Ura-Gua-3' by making Watson-Crick-like hydrogen bonds with 5'-Cyt-Ade-3'. Sequence conservation suggests that fragile X mental retardation results from perturbation of RNA binding by the FMR1 protein.

Original languageEnglish (US)
Pages (from-to)323-332
Number of pages10
JournalCell
Volume100
Issue number3
DOIs
StatePublished - Feb 4 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Sequence-specific RNA binding by a Nova KH domain: Implications for paraneoplastic disease and the fragile X syndrome'. Together they form a unique fingerprint.

  • Cite this