RESUMEN
Cancer cells rely on metabolic reprogramming to sustain the prodigious energetic requirements for rapid growth and proliferation. Glutamine metabolism is frequently dysregulated in cancers and is being exploited as a potential therapeutic target. Using CRISPR/Cas9 interference (CRISPRi) screening, we identified TARBP1 (TAR (HIV-1) RNA Binding Protein 1) as a critical regulator involved in glutamine reliance of cancer cell. Consistent with this discovery, TARBP1 amplification and overexpression are frequently observed in various cancers. Knockout of TARBP1 significantly suppresses cell proliferation, colony formation and xenograft tumor growth. Mechanistically, TARBP1 selectively methylates and stabilizes a small subset of tRNAs, which promotes efficient protein synthesis of glutamine transporter-ASCT2 (also known as SLC1A5) and glutamine import to fuel the growth of cancer cell. Moreover, we found that the gene expression of TARBP1 and ASCT2 are upregulated in combination in clinical cohorts and their upregulation is associated with unfavorable prognosis of HCC (hepatocellular carcinoma). Taken together, this study reveals the unexpected role of TARBP1 in coordinating the tRNA availability and glutamine uptake during HCC progression and provides a potential target for tumor therapy.
RESUMEN
Table grapes are susceptible to external pathogens during postharvest storage. The resulting continuous oxidative stress causes damage and aging, thereby reducing the defense against disease. In this study, the effect of biocontrol yeast T-2 on the storage performance of grapes was evaluated. After T-2 treatment, the grapefruits rot rate and lesion diameter caused by Botrytis cinerea (B. cinerea) were significantly decreased at 2-5 days after inoculation (DAI). Additionally, the browning rate and shedding rate of grapefruit during storage were significantly reduced at 2-5 DAI, and the weight loss rate was significantly reduced at 3-5 DAI. The decreased malondialdehyde (MDA) content in grapefruits at 1-5 DAI with T-2 indicated a reduction in oxidative damage. Furthermore, the activities of antioxidant enzymes such as peroxidase (POD), catalase (CAT), phenylalanin ammonia-lyase (PAL) were significantly increased during most storage time after being treated with T-2. Moreover, the contents of total phenolics and flavonoids and the expression levels of key enzyme genes in metabolic pathways were increased after T-2 treatment during most postharvest storage time, providing evidence that T-2 changed the biological process of phenolic flavonoid metabolism. The increase in enzymatic and nonenzymatic antioxidants after treatment with T-2 reflected the strengthening of the antioxidant system, hence postponing fruit senescence and promoting storage performance under the stress of B. cinerea.
RESUMEN
Cohesin regulates sister chromatid cohesion but also contributes to chromosome folding by promoting the formation of chromatin loops, a process mediated by loop extrusion. Although PDS5 regulates cohesin dynamics on chromatin, the exact function of PDS5 in cohesin-mediated chromatin looping remains unclear. Two paralogs of PDS5 exist in vertebrates, PDS5A and PDS5B. Here we show that PDS5A and PDS5B co-localize with RAD21 and CTCF at loop anchors. Rapid PDS5A or PDS5B degradation in liver cancer cells using an inducible degron system reduces chromatin loops and increases loop size. RAD21 enrichment at loop anchors is decreased upon depletion of PDS5A or PDS5B. PDS5B loss also reduces CTCF signals at loop anchors and has a stronger effect on loop enlargement compared with PDS5A. Co-depletion of PDS5A and PDS5B reduces RAD21 levels at loop anchors although the amount of cohesin on chromatin is increased. Our study provides insight into how PDS5 proteins regulate cohesin-mediated chromatin looping.