A single nucleotide change in the c-myc internal ribosome entry segment leads to enhanced binding of a group of protein factors

Abstract

A 340 nucleotide section of the c-myc 5' untranslated region (UTR) contains an internal ribosome entry segment. We have described previously a mutation in this region of RNA in cell lines derived from patients with multiple myeloma (MM) which exhibit increased expression of c-myc protein by an aberrant translational mechanism. In this study we show by electrophoretic mobility shift assays (EMSA), north-western blotting and UV cross-linking that radiolabelled c-myc 5' UTR RNA transcripts which harbour the mutation cause enhanced binding of cellular proteins. In addition, we also demonstrate that an MM derived cell line possesses an altered repertoire of RNA binding proteins. Our data suggest that the deregulated expression of c-myc in MM could result both from the effect of the mutation and the additional proteins which are present in these cell types.