tRF-3021a Promotes Apoptosis Resistance and Global Protein Synthesis in Cancer Cell Lines

tRNA-derived fragments (tRFs) are a relatively recently discovered class of small RNAs implicated in gene-regulation, particularly behaving as microRNA to degrade target mRNAs with seed-sequence matches, but there have been very few reports of a clear phenotypic role of these small RNAs in cancer cell growth and other properties. Here we report that in three different cancer cell lineages, tRF-3009a, tRF-3021a and tRF-3030a are required for cell invasion and migration. Of the three tRFs, tRF-3021a was uniquely required for cell proliferation and suppression of apoptosis. Interestingly, tRF-3021a knockdown decreases global protein synthesis prior to and independent of apoptosis in a number of cancer cell lines of different lineages. Mutation of tRF-3021a shows that the effect on protein synthesis is very dependent on specific sequences in the tRF. RNA-seq reveals that the results cannot be explained by tRF-3021a decreasing the levels of target mRNAs that carry seed sequence matches with the tRF. These data indicate that tRF-3021a supports cancer cell survival and particularly protein synthesis while promoting cellular invasion and migration. Implications: tRF-3021a promotes malignant cell phenotypes, sustains global protein synthesis and prevents spontaneous apoptosis.