Global Translational Impacts of the Loss of the tRNA Modification t6A in Yeast

The universal tRNA modification t6A is found at position 37 of nearly all tRNAs decoding ANN codons. The importance of t6A in decoding has been studied for the past 40 years, but the cellular role has remained unclear. In this work, we examined the genome-wide effect to translation during the absence of t6A. In accordance with the previous experiments using single gene reporters, absence of t6A led to a increase of upstream non-AUG initiation of translation and increased translation ambiguities. Surprisingly, absence of t6A did not lead to a global and cataclysmic frame-shifting, but instead occurred only in a few genes. Restoration of protein homeostasis through the overexpression of Unfolded Protein Response (UPR) factors or the addition of L-homoserine suppressed the slow growth phenotype seen in t6A-defcient strains. 4 samples