Project description:Understanding the molecular mechanisms underlying the regulation of gene expression during skeletal muscle cell proliferation and differentiation is critical to the development of novel therapeutic targets to treat muscle disorders. In this study, we report the identification and characterization of mt-Ty 5’tiRNAs, tRNA-derived fragments (tiRNAs) we identified in skeletal muscle. mt-Ty 5’tiRNAs are found in the nucleus and mitochondria of skeletal muscle cells and its expression is induced by angiogenin. Gapmer-mediated inhibition of tiRNAs in skeletal muscle C2C12 myoblasts resulted in mitochondrial fragmentation. We also observed a decrease in cell proliferation and myogenic differentiation upon mt-Ty 5’tiRNA inhibition; consistent with this observation, RNA-seq and transcriptome analyses revealed that skeletal muscle cell differentiation and cell proliferation pathways were also downregulated. Conversely, overexpression of mt-Ty 5’tiRNAs in C2C12 cells led to a reversal of the transcriptional trends noted for these pathway genes. These data reveal mt-Ty 5’tiRNAs as a skeletal muscle enriched tiRNA that plays important roles in myoblast proliferation and differentiation. Our study also highlights the potential for the development of tiRNAs as novel therapeutic targets for muscle related diseases
Project description:endogenous small RNAs from Chlamydomonas reinhardtii strain J3(mt-) vegetative cells Keywords: High throughput 454 small RNA sequencing
Project description:To investigate the effects of NFKB signaling, RNA-seq analysis was performed on both Jurkat and MT-2 cells. It was observed that either NFKB1 or NFKB2 knockout could alter the gene expression profile in MT-2 cells compared to Jurkat cells. Gene expression profiles of NFKB1/NFKB2 knockout Jurkat cells were compared to the mock edited Jurkat cells. On the other hand, it was hypothesized that the gene expression profile of MT-2 cells can be more drastically altered by NFKB1 or NFKB2 knockout. NFKB2 knockout MT-2 cells exhibited a unique gene expression profile compared to those of NFKB1 knockout MT-2 cells and mock edited MT-2 cells.