The myotonic dystrophy type 2 protein ZNF9 is part of an ITAF complex that promotes Cap-independent translation

Robert V Gerbasi, Andrew J. Link*

*Corresponding author for this work

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The 5′-untranslated region of the ornithine decarboxylase (ODC) mRNA contains an internal ribosomal entry site (IRES). Mutational analysis of the ODC IRES has led to the identification of sequences necessary for cap-independent translation of the ODC mRNA. To discover novel IRES trans-acting factors (ITAFs), we performed a proteomics screen for proteins that regulate ODC translation using the wild-type ODC mRNA and a mutant version with an inactive IRES. We identified two RNA-binding proteins that associate with the wild-type ODC IRES but not the mutant IRES. One of these RNA-binding proteins, PCBP2, is an established activator of viral and cellular IRESs. The second protein, ZNF9 (myotonic dystrophy type 2 protein), has not been shown previously to bind IRES-like elements. Using a series of biochemical assays, we validated the interaction of these proteins with ODC mRNA. Interestingly ZNF9 and PCBP2 biochemically associated with each other and appeared to function as part of a larger holo-ITAF ribonucleoprotein complex. Our functional studies showed that PCBP2 and ZNF9 stimulate translation of the ODC IRES. Importantly these results may provide insight into the normal role of ZNF9 and why ZNF9 mutations cause myotonic dystrophy.

Original languageEnglish (US)
Pages (from-to)1049-1058
Number of pages10
JournalMolecular and Cellular Proteomics
Volume6
Issue number6
DOIs
StatePublished - Jun 2007

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'The myotonic dystrophy type 2 protein ZNF9 is part of an ITAF complex that promotes Cap-independent translation'. Together they form a unique fingerprint.

Cite this