Identification of the NAD+-binding fold of glyceraldehyde-3-phosphate dehydrogenase as a novel RNA-binding domain

Eszter Nagy, Tamás Henics, Mária Eckert, Attila Miseta, Robert N. Lightowlers, Miklós Kellermayer

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

There is growing evidence that metabolic enzymes may act as multifunctional proteins performing diverse roles in cellular metabolism. Among these functions are the RNA-binding activities of NAD+-dependent dehydrogenases. Previously, we have chartacterized the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an RNA-binding protein with preference to adenine-uracil-rich sequences. In this study, we used GST-GAPDH fusion proteins generated by deletion mutagenesis to search for the RNA binding domain. We established that the N-terminal 43 amino acid residues of GAPDH, which correspond to the first mononucleotide-binding domain of the NAD+-binding fold is sufficient to confer RNA-binding. We also provide evidence that this single domain, although it retains most of the RNA-binding activity, loses sequence specificity. Our results suggest a molecular basis for RNA-recognition by NAD+-dependent dehydrogenases and (di)nucleotide-binding metabolic enzymes that had been reported to have RNA-binding activity with different specificity. To support this prediction we also identified other members of the family of NAD+-dependent dehydrogenases with no previous history of nucleic acid binding as RNA binding proteins in vitro. Based on our findings we propose the addition of the NAD+-binding domain to the list of RNA binding domains/motifs. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalBiochemical and biophysical research communications
Volume275
Issue number2
DOIs
Publication statusPublished - Aug 28 2000

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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