The tRNA Gm18 methyltransferase TARBP1 promotes hepatocellular carcinoma progression via metabolic reprogramming of glutamine.

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.

Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia.

Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain. In this study, the molecular mechanism of DAZ is identified, which is unknown since it is identified 40 years ago because of the lack of a suitable model. Using clinical samples and cell models, it is shown that DAZ plays an important role in spermatogenesis and that loss of DAZ is associated with defective proliferation of c-KIT-positive spermatogonia in patients with AZFc_del. Mechanistically, it is shown that knockdown of DAZ significantly downregulated global translation and subsequently decreased cell proliferation. Furthermore, DAZ interacted with PABPC1 via the DAZ repeat domain to regulate global translation. DAZ targeted mRNAs that are involved in cell proliferation and cell cycle phase transition. These findings indicate that DAZ is a master translational regulator and essential for the maintenance of spermatogonia. Loss of DAZ may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure.

Biocontrol yeast T-2 improves the postharvest disease resistance of grape by stimulation of the antioxidant system.

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.

Regulation of cohesin-mediated chromosome folding by PDS5 in mammals.

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.

Enabling robust and hour-level organic long persistent luminescence from carbon dots by covalent fixation.

The first carbon dot (CD)-based organic long persistent luminescence (OLPL) system exhibiting more than 1 h of duration was developed. In contrast to the established OLPL systems, herein, the reported CDs-based system (named m-CDs@CA) can be facilely and effectively fabricated using a household microwave oven, and more impressively, its LPL can be observed under ambient conditions and even in aqueous media. XRD and TEM characterizations, afterglow decay, time-resolved spectroscopy, and ESR analysis were performed, showing the successful composition of CDs and CA, the formation of exciplexes and long-lived charged-separated states. Further studies suggest that the production of covalent bonds between CA and CDs plays pivotal roles in activating LPL and preventing its quenching from oxygen and water. To the best of our knowledge, this is a very rare example of an OLPL system that exhibits hour-level afterglow under ambient conditions. Finally, applications of m-CDs@CA in glow-in-the-dark paints for emergency signs and multicolored luminous pearls were preliminarily demonstrated. This work may provide new insights for the development of rare-earth-free and robust OLPL materials.

Green and Near-Infrared Dual-Mode Afterglow of Carbon Dots and Their Applications for Confidential Information Readout.

Near-infrared (NIR), particularly NIR-containing dual-/multi-mode afterglow, is very attractive in many fields of application, but it is still a great challenge to achieve such property of materials. Herein, we report a facile method to prepare green and NIR dual-mode afterglow of carbon dots (CDs) through in situ embedding o-CDs (being prepared from o-phenylenediamine) into cyanuric acid (CA) matrix (named o-CDs@CA). Further studies reveal that the green and NIR afterglows of o-CDs@CA originate from thermal activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP) of o-CDs, respectively. In addition, the formation of covalent bonds between o-CDs and CA, and the presence of multiple fixation and rigid effects to the triplet states of o-CDs are confirmed to be critical for activating the observed dual-mode afterglow. Due to the shorter lifetime and insensitiveness to human vision of the NIR RTP of o-CDs@CA, it is completely covered by the green TADF during directly observing. The NIR RTP signal, however, can be readily captured if an optical filter (cut-off wavelength of 600 nm) being used. By utilizing these unique features, the applications of o-CDs@CA in anti-counterfeiting and information encryption have been demonstrated with great confidentiality. Finally, the as-developed method was confirmed to be applicable to many other kinds of CDs for achieving or enhancing their afterglow performances.

Photo-Stimulated Polychromatic Room Temperature Phosphorescence of Carbon Dots.

Single-component multicolor luminescence, particularly phosphorescence materials are highly attractive both in numerous applications and in-depth understanding the light-emission processes, but formidable challenges still exist for preparing such materials. Herein, a very facile approach is reported to synthesize carbon dots (CDs) (named MP-CDs) that exhibit multicolor fluorescence (FL), and more remarkably, multicolor long-lived room temperature phosphorescence (RTP) under ambient conditions. The FL and RTP colors of the CDs powder are observed to change from blue to green and cyan to yellow, respectively, with the excitation wavelength shifting from 254 to 420 nm. Further studies demonstrate that the multicolor emissions can be attributed to the existence of multiple emitting centers in the CDs and the relatively higher reaction temperature plays a critical role for achieving RTP. Given the unique optical properties, a preliminary application of MP-CDs in advanced anti-counterfeiting is presented. This study not only proposes a strategy to prepare photo-stimulated multicolor RTP materials, but also reveals great potentials of CDs in exploiting novel optical materials with unique properties.

Visible-Light-Excited Room Temperature Phosphorescent Carbon Dots.

Carbon dots (CDs) with a room temperature phosphorescent (RTP) feature have attracted considerable interest in recent years due to their fundamental importance and promising applications. However, the reported matrix-free RTP CDs only show short-wavelength (green to yellow) emissions and have to be triggered by ultraviolet (UV) light (below 400 nm), limiting their applications in certain fields. Herein, visible-light-excited matrix-free RTP CDs (named AA-CDs) with a long-wavelength (orange) emission are reported for the first time. The AA-CDs can be facilely prepared via a microwave heating treatment of L-aspartic acid (AA) in the presence of ammonia and they emit unique orange RTP in the solid state with visible light (420 nm) excitation just being switched off. Through the studies of the carbonization process, the C=O and C=N containing moieties in the AA-CDs are confirmed to be responsible for the observed RTP emission. Finally, the applications of AA-CDs in information encryption and anti-counterfeiting were preliminarily demonstrated.