A tRNA-derived microRNA modulates the DNA damage response and is downregulated in B cell lymphoma

Sequencing studies from several model systems have suggested that diverse and abundant small RNAs may derive from tRNA, but the function of these molecules remains undefined. Here we demonstrate that one such tRNA fragment, cloned from human B cells and designated CU1276, in fact possesses the functional characteristics of a microRNA, including a DICER1-dependent biogenesis, physical association with Argonaute proteins, and the ability to repress mRNA transcripts in a sequence-specific manner. The gene expression profiling undertaken for this study was done in order to assay mRNA-level changes in 293T cells upon modulation of CU1276 levels, and thereby to identify direct targets of this sequence. Ultimately, we fully validated the endogenous gene RPA1 as a CU1276 target. This study includes four biological replicates each of the following groups: 293T transiently transfected with empty vector, 293T transiently transfected with chr1.tRNA68-Gly(GCC) expressing vector, and 293T transiently transfected with CU1276 hairpin expressing vector.