Roles and regulation of tRNA-derived small RNAs in animals.

A growing class of small RNAs, known as tRNA-derived RNAs (tdRs), tRNA-derived small RNAs or tRNA-derived fragments, have long been considered mere intermediates of tRNA degradation. These small RNAs have recently been implicated in an evolutionarily conserved repertoire of biological processes. In this Review, we discuss the biogenesis and molecular functions of tdRs in mammals, including tdR-mediated gene regulation in cell metabolism, immune responses, transgenerational inheritance, development and cancer. We also discuss the accumulation of tRNA-derived stress-induced RNAs as a distinct adaptive cellular response to pathophysiological conditions. Furthermore, we highlight new conceptual advances linking RNA modifications with tdR activities and discuss challenges in studying tdR biology in health and disease.

Highly Flexible and Acid-Alkali Resistant TiN Nanomesh Transparent Electrodes for Next-Generation Optoelectronic Devices.

Transparent electrodes are vital for optoelectronic devices, but their development has been constrained by the limitations of existing materials such as indium tin oxide (ITO) and newer alternatives. All face issues of robustness, flexibility, conductivity, and stability in harsh environments. Addressing this challenge, we developed a flexible, low-cost titanium nitride (TiN) nanomesh transparent electrode showcasing exceptional acid-alkali resistance. The TiN nanomesh electrode, created by depositing a TiN coating on a naturally cracked gel film substrate via a sputtering method, maintains a stable electrical performance through thousands of bending cycles. It exhibits outstanding chemical stability, resisting strong acid and alkali corrosion, which is a key hurdle for current electrodes when in contact with acidic/alkaline materials and solvents during device fabrication. This, coupled with superior light transmission and conductivity (88% at 550 nm with a sheet resistance of ∼200 Ω/sq), challenges the reliance on conventional materials. Our TiN nanomesh electrode, successfully applied in electric heaters and electrically controlled thermochromic devices, offers broad potential beyond harsh environment applications. It enables alternative possibilities for the design and fabrication of future optoelectronics for advancements in this pivotal field.

Biallelic variants in NSUN6 cause an autosomal recessive neurodevelopmental disorder.

PURPOSE: 5-methylcytosine RNA modifications are driven by NSUN methyltransferases. Although variants in NSUN2 and NSUN3 were associated with neurodevelopmental diseases, the physiological role of NSUN6 modifications on transfer RNAs and messenger RNAs remained elusive. METHODS: We combined exome sequencing of consanguineous families with functional characterization to identify a new neurodevelopmental disorder gene. RESULTS: We identified 3 unrelated consanguineous families with deleterious homozygous variants in NSUN6. Two of these variants are predicted to be loss-of-function. One maps to the first exon and is predicted to lead to the absence of NSUN6 via nonsense-mediated decay, whereas we showed that the other maps to the last exon and encodes a protein that does not fold correctly. Likewise, we demonstrated that the missense variant identified in the third family has lost its enzymatic activity and is unable to bind the methyl donor S-adenosyl-L-methionine. The affected individuals present with developmental delay, intellectual disability, motor delay, and behavioral anomalies. Homozygous ablation of the NSUN6 ortholog in Drosophila led to locomotion and learning impairment. CONCLUSION: Our data provide evidence that biallelic pathogenic variants in NSUN6 cause one form of autosomal recessive intellectual disability, establishing another link between RNA modification and cognition.

A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription.

Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial-mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA-modifying enzyme provides a new perspective for understanding epitranscriptomic regulation.

The occurrence order and cross-talk of different tRNA modifications.

Chemical modifications expand the composition of RNA molecules from four standard nucleosides to over 160 modified nucleosides, which greatly increase the complexity and utility of RNAs. Transfer RNAs (tRNAs) are the most heavily modified cellular RNA molecules and contain the largest variety of modifications. Modification of tRNAs is pivotal for protein synthesis and also precisely regulates the noncanonical functions of tRNAs. Defects in tRNA modifications lead to numerous human diseases. Up to now, more than 100 types of modifications have been found in tRNAs. Intriguingly, some modifications occur widely on all tRNAs, while others only occur on a subgroup of tRNAs or even only a specific tRNA. The modification frequency of each tRNA is approximately 7% to 25%, with 5-20 modification sites present on each tRNA. The occurrence and modulation of tRNA modifications are specifically noticeable as plenty of interplays among different sites and modifications have been discovered. In particular, tRNA modifications are responsive to environmental changes, indicating their dynamic and highly organized nature. In this review, we summarized the known occurrence order, cross-talk, and cooperativity of tRNA modifications.

Si2BN monolayers as promising candidates for hydrogen storage.

Hydrogen storage properties of the pure Si2BN monolayer were studied using density functional theory calculations. The interaction of H2 molecules with the Si2BN monolayer is weak and of electrostatic nature. The average hydrogen adsorption energies are within the ideal range of practical applications (0.187-0.214 eV), and the consecutive adsorption energies indicate that the spontaneous adsorption of H2 molecules on the Si2BN monolayer can occur. The hydrogen gravimetric density of the periodic Si2BN monolayer reaches 8.5 wt%, which exceeds the standard of 6.0 wt% set by the US Department of Energy (DOE) by the year 2020. The estimated desorption temperatures show the desirable properties for the long term recycling of the Si2BN storage medium. Thus, our results show that the Si2BN monolayer is a promising candidate for molecular hydrogen storage.