Abstract B14: Evidence that Tma20 and Tma22 do not promote translation re-initiation in yeast

Abstract

Abstract Translation Machinery Association 20 (Tma20) and Tma22 are two conserved proteins which form a complex involved in translation initiation. The human homolog of TMA20 is an oncogene, originally identified in a T-cell lymphoma and has been shown to induce cell proliferation. Tma20 and Tma22 homologs in Drosophila have been shown to promote translation of mRNAs which contain uORFs by promoting translation re-initiation. uORFs serve as major regulators of gene expression, repressing translation. In yeast Tma20 and Tma22 have recently been shown to have a role in telomere biology by decreasing fitness of cells with uncapped telomeres. To understand how Tma20 and Tma22 affect growth of cells with uncapped telomeres we have investigated translation re-initiation in yeast using new luciferase reporter constructs. Using transcript leader sequences from 22 genes we showed that, as expected, the majority of uORFs repressed expression but found no evidence to suggest that Tma20 or Tma22 promote translation re-initiation in 21 of these genes. However our data suggests that Tma20 and Tma22 inhibit translation re-initiation of the remaining gene, BRE4. Our data suggests that the function of Tma20 and Tma22 is not conserved from Drosophila to yeast. Our finding that Tma20 and Tma22 inhibit translation re-initiation on BRE4 is in agreement with studies in mammalian cells which have shown that Tma20 and Tma22 promote the dissociation of 40S ribosomal subunit from mRNA following translation termination. Our data suggests that perhaps the human homologs of Tma20 and Tma22 may not promote translation re-initiation as has previously been assumed. Citation Format: Victoria Torrance, David Lydall. Evidence that Tma20 and Tma22 do not promote translation re-initiation in yeast. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B14.