Characterization of programmed -1 ribosomal frameshift signals in the interleukin 2 receptor gamma mRNA

Abstract

Programmed -1 ribosomal frameshift (-1 PRF) signals are predicted to be present in ~10% of eukaryotic mRNA, suggesting a conserved role for -1 PRF in eukaryotic mRNA translation. This work focuses on -1 PRF in the interleukin 2 receptor gamma (IL2RG) mRNA. IL2RG is a component of receptors for six cytokines responsible for lymphocyte proliferation and differentiation. Altered expression of IL2RG is linked to immunodeficiency and lymphoma. We verified that the IL2RG mRNA has one potential -1 PRF signal in exon 3 that stimulates -1 frameshifting and a second in exon 8 that is definitively a -1 PRF signal. Both of these signals redirect the ribosome to a premature termination codon, suggesting -1 PRF alters IL2RG expression via NMD. Testing the effect of cancer patient associated mutations discovered in the exon 8 -1 PRF signal may elucidate a role for IL2RG -1 PRF in normal physiology and pathological phenotypes.