Multiple roles of CTDK-I throughout the cell.

The heterotrimeric carboxy-terminal domain kinase I (CTDK-I) in yeast is a cyclin-dependent kinase complex that is evolutionally conserved throughout eukaryotes and phosphorylates the C-terminal domain of the largest subunit of RNA polymerase II (RNApII) on the second-position serine (Ser2) residue of YSPTSPS heptapeptide repeats. CTDK-I plays indispensable roles in transcription elongation and transcription-coupled processing, such as the 3'-end processing of nascent mRNA transcripts. However, recent studies have revealed additional roles of CTDK-I beyond its primary effect on transcription by RNApII. Here, we describe recent advances in the regulation of genomic stability and rDNA integrity by CTDK-I and highlight the previously underappreciated cellular roles of CTDK-I in rRNA synthesis by RNA polymerase I and translational initiation and elongation. These multiple roles of CTDK-I throughout the cell expand our understanding of how this complex functions to coordinate diverse cellular processes through gene expression and how the human orthologue exerts its roles in diseased states such as tumorigenesis.

Design and evaluation of an intelligent physical examination system in improving the satisfaction of patients with chronic disease.

Background: and Purpose: Enhancing patient satisfaction remains crucial for healthcare quality. The utilization of artificial intelligence (AI) in the Internet of Health Things (loHT) can streamline the medical examination process. Most Traditional Chinese Medicine (TCM) examinations are non-invasive and contribute significantly to patient satisfaction. Our aim was to establish an intelligent physical examination system that amalgamates TCM and Western medicine and to conduct a preliminary investigation into its effectiveness in enhancing the satisfaction of patients with chronic diseases. Materials and methods: Experts from clinical departments, the equipment department, and the software development department were invited to participate in group discussions to determine the design principles and organizational structure of the intelligent physical examination system. This system integrates TCM and Western medicine. We compared the satisfaction levels of patients examined using the intelligent physical examination system with those examined using the traditional medical examination system. Results: An intelligent physical examination system, combining TCM and Western medicine, was developed. A total of 106 patients were finally enrolled (intelligent group vs. control group) to evaluate satisfaction. There were no statistically significant differences between the intelligent group and the control group in age, gender, education, or income level. We identified significant differences in five aspects of satisfaction: 1) the physical examination environment; 2) the attitude and responsiveness of doctors; 3) the attitude and responsiveness of nurses; 4) the effectiveness of obtaining results; and 5) the information regarding physical examination and medical advice (p < 0.05). Furthermore, these differences remained statistically significant even after adjusting for age, gender, education, and income level. Conclusions: The intelligent physical examination system effectively capitalized on the advantages of combining AI with the integration of TCM and Western medicine, substantially optimizing the medical examination process. In comparison to the traditional physical examination system, the intelligent system significantly enhanced patient satisfaction. Future improvements could involve integrating chronic disease follow-up technology into the system.

Tho2-mediated escort of Nrd1 regulates the expression of aging-related genes.

The relationship between aging and RNA biogenesis and trafficking is attracting growing interest, yet the precise mechanisms are unknown. The THO complex is crucial for mRNA cotranscriptional maturation and export. Herein, we report that the THO complex is closely linked to the regulation of lifespan. Deficiencies in Hpr1 and Tho2, components of the THO complex, reduced replicative lifespan (RLS) and are linked to a novel Sir2-independent RLS control pathway. Although transcript sequestration in hpr1Δ or tho2Δ mutants was countered by exosome component Rrp6, loss of this failed to mitigate RLS defects in hpr1Δ. However, RLS impairment in hpr1Δ or tho2Δ was counteracted by the additional expression of Nrd1-specific mutants that interacted with Rrp6. This effect relied on the interaction of Nrd1, a transcriptional regulator of aging-related genes, including ribosome biogenesis or RNA metabolism genes, with RNA polymerase II. Nrd1 overexpression reduced RLS in a Tho2-dependent pathway. Intriguingly, Tho2 deletion mirrored Nrd1 overexpression effects by inducing arbitrary Nrd1 chromatin binding. Furthermore, our genome-wide ChIP-seq analysis revealed an increase in the recruitment of Nrd1 to translation-associated genes, known to be related to aging, upon Tho2 loss. Taken together, these findings underscore the importance of Tho2-mediated Nrd1 escorting in the regulation of lifespan pathway through transcriptional regulation of aging-related genes.

The RNA polymerase II Rpb4/7 subcomplex regulates cellular lifespan through an mRNA decay process.

In budding yeast, a highly conserved heterodimeric protein complex that is composed of the Rpb4 and Rpb7 proteins within RNA polymerase II shuttles between the nucleus and cytoplasm where it coordinates various steps of gene expression by associating with mRNAs. Although distinct stages of gene expression potentially contribute to the regulation of cellular lifespan, little is known about the underlying mechanisms. Here, we addressed the role of the dissociable Rpb4/7 heterodimeric protein complex in the regulation of replicative lifespan during various stages of gene expression in the yeast Saccharomyces cerevisiae. We observed that the loss of Rpb4 resulted in a shortened lifespan. In contrast, we found that defects in the dissociation of Rpb4/7 from the RNA polymerase core complex and in translation initiation steps affected by Rpb4/7 did not impact lifespan. Tandem affinity purification experiments demonstrated that Rpb7 physically associates with Tpk2 and Pat1, which are both implicated in mRNA degradation. Consistent with this data, the loss of the mRNA decay regulators Pat1 and Dhh1 reduced the cellular lifespan. In summary, our findings further reinforce the pivotal role of Rpb4/7 in the coordination of distinct steps of gene expression and suggest that among the many stages of gene expression, mRNA decay is a critical process that is required for normal replicative lifespan.

The Spt7 subunit of the SAGA complex is required for the regulation of lifespan in both dividing and nondividing yeast cells.

Spt7 belongs to the suppressor of Ty (SPT) module of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex and is known as the yeast ortholog of human STAF65γ. Spt7 lacks intrinsic enzymatic activity but is responsible for the integrity and proper assembly of the SAGA complex. Here, we determined the role of the SAGA Spt7 subunit in cellular aging. We found that Spt7 was indispensable for a normal lifespan in both dividing and nondividing yeast cells. In the quiescent state of cells, Spt7 was required for the control of overall mRNA levels. In mitotically active cells, deletion of the SPT module had little effect on the recombination rate within heterochromatic ribosomal DNA (rDNA) loci, but loss of Spt7 profoundly elevated the plasmid-based DNA recombination frequency. Consistently, loss of Spt7 increased spontaneous Rad52 foci by approximately two-fold upon entry into S phase. These results provide evidence that Spt7 contributes to the regulation of the normal replicative lifespan (RLS) and chronological lifespan (CLS), possibly by controlling the DNA recombination rate and overall mRNA expression. We propose that the regulation of SAGA complex integrity by Spt7 might be involved in the conserved regulatory pathway for lifespan regulation in eukaryotes.

Symmetric dimethylation on histone H4R3 associates with histone deacetylation to maintain properly polarized cell growth.

Yeast Hsl7 is recognized as a homolog of human arginine methyltransferase 5 (PRMT5) and shows type II PRMT activity by forming symmetric dimethylarginine residues on histones. Previously, we reported that Hsl7 is responsible for in vivo symmetric dimethylation on histone H4 arginine 3 (H4R3me2s) in a transcriptionally repressed state, possibly in association with histone deacetylation by Rpd3. Here, we investigated the function of Hsl7 during cell cycle progression. We found that the accumulation of Hsl7-mediated H4R3me2s is maintained by the histone deacetylase Rpd3 during transcriptional repression and that the low level of H4R3me2s is required for proper asymmetric cell growth during cell division. Our results suggest that the hypoacetylated state of histones is connected to the function of Hsl7 in regulating properly polarized cell growth during cell division and provide new insight into the epigenetic modifications that are important for cell cycle morphogenesis checkpoint control based on the repressive histone crosstalk between symmetric arginine methylation of H4 and histone deacetylation.

Effects of Different Hosts on Bacterial Communities of Parasitic Wasp Nasonia vitripennis.

Parasitism is a special interspecific relationship in insects. Unlike most other ectoparasites, Nasonia vitripennis spend most of its life cycle (egg, larvae, pupae, and early adult stage) inside the pupae of flies, which is covered with hard puparium. Microbes play important roles in host development and help insect hosts to adapt to various environments. How the microbes of parasitic wasp respond to different fly hosts living in such close relationships motivated this investigation. In this study, we used N. vitripennis and three different fly pupa hosts (Lucilia sericata, Sarcophaga marshalli, and Musca domestica) to address this question, as well as to illustrate the potential transfer of bacteria through the trophic food chains. We found that N. vitripennis from different fly pupa hosts showed distinct microbiota, which means that the different fly hosts could affect the bacterial communities of their parasitic wasps. Some bacteria showed potential horizontal transfer through the trophic food chains, from the food through the fly to the parasitic wasp. We also found that the heritable endosymbiont Wolbachia could transferred from the fly host to the parasite and correlated with the bacterial communities of the corresponding parasitic wasps. Our findings provide new insight to the microbial interactions between parasite and host.

Yeast symmetric arginine methyltransferase Hsl7 has a repressive role in transcription.

Protein arginine methylation, an evolutionarily conserved post-translational modification, serves critical cellular functions by transferring a methyl group to a variety of substrates, including histones and some transcription factors. In budding yeast, Hsl7 (histone synthetic lethal 7) displays type II PRMT (protein arginine methyltransferase) activity by generating symmetric dimethylarginine residues on histone H2A in vitro. However, identification of the in vivo substrate of Hsl7 and how it contributes to important cellular processes remain largely unexplored. In the present study, we show that Hsl7 has a repressive role in transcription. We found that Hsl7 is responsible for in vivo symmetric dimethylation of histone H4 arginine 3 (H4R3me2s) in a transcriptionally repressed state. Tandem affinity purification further demonstrated that Hsl7 physically interacts with histone deacetylase Rpd3, and both similarly repress transcription. Our results suggest that H4R3me2s generation by the type II PRMT Hsl7 is required for transcriptional repression, possibly in cooperation with histone deacetylation by Rpd3.