Protein-RNA and protein-protein recognition by dual KH1/2 domains of the neuronal splicing factor Nova-1. Academic Article uri icon

Overview

abstract

  • Nova onconeural antigens are neuron-specific RNA-binding proteins implicated in paraneoplastic opsoclonus-myoclonus-ataxia (POMA) syndrome. Nova harbors three K-homology (KH) motifs implicated in alternate splicing regulation of genes involved in inhibitory synaptic transmission. We report the crystal structure of the first two KH domains (KH1/2) of Nova-1 bound to an in vitro selected RNA hairpin, containing a UCAG-UCAC high-affinity binding site. Sequence-specific intermolecular contacts in the complex involve KH1 and the second UCAC repeat, with the RNA scaffold buttressed by interactions between repeats. Whereas the canonical RNA-binding surface of KH2 in the above complex engages in protein-protein interactions in the crystalline state, the individual KH2 domain can sequence-specifically target the UCAC RNA element in solution. The observed antiparallel alignment of KH1 and KH2 domains in the crystal structure of the complex generates a scaffold that could facilitate target pre-mRNA looping on Nova binding, thereby potentially explaining Nova's functional role in splicing regulation.

publication date

  • July 13, 2011

Research

keywords

  • Antigens, Neoplasm
  • Nerve Tissue Proteins
  • Neurons
  • Opsoclonus-Myoclonus Syndrome
  • RNA Precursors
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Synaptic Transmission

Identity

PubMed Central ID

  • PMC3134789

Scopus Document Identifier

  • 79960189594

Digital Object Identifier (DOI)

  • 10.1016/j.str.2011.05.002

PubMed ID

  • 21742260

Additional Document Info

volume

  • 19

issue

  • 7