Biomolecular condensates and disease pathogenesis.

Biomolecular condensates or membraneless organelles (MLOs) formed by liquid-liquid phase separation (LLPS) divide intracellular spaces into discrete compartments for specific functions. Dysregulation of LLPS or aberrant phase transition that disturbs the formation or material states of MLOs is closely correlated with neurodegeneration, tumorigenesis, and many other pathological processes. Herein, we summarize the recent progress in development of methods to monitor phase separation and we discuss the biogenesis and function of MLOs formed through phase separation.

Fruit Extracts Upregulate Telomerase Activity and Ameliorate Cell Replicative Senescence.

Anti-aging functional foods benefit the elderly. Telomeres are chromosomal ends that maintain genome stability extended by telomerase catalytic subunit TERT. Due to the end-replication problem, telomeres shorten after each cell cycle without telomerase in most human cells, and eventually the cell enters the senescence stage.

Identification and Validation of eRNA as a Prognostic Indicator for Cervical Cancer.

The survival of CESC patients is closely related to the expression of enhancer RNA (eRNA). In this work, we downloaded eRNA expression, clinical, and gene expression data from the TCeA and TCGA portals. A total of 7936 differentially expressed eRNAs were discovered by limma analysis, and the relationship between these eRNAs and survival was analyzed by univariate Cox hazard analysis, LASSO regression, and multivariate Cox hazard analysis to obtain an 8-eRNA model.

The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb.

Rheb is a small G protein that functions as the direct activator of the mechanistic target of rapamycin complex 1 (mTORC1) to coordinate signaling cascades in response to nutrients and growth factors. Despite extensive studies, the guanine nucleotide exchange factor (GEF) that directly activates Rheb remains unclear, at least in part due to the dynamic and transient nature of protein-protein interactions (PPIs) that are the hallmarks of signal transduction. Here, we report the development of a rapid and robust proximity labeling system named Pyrococcus horikoshii biotin protein ligase (PhBPL)-assisted biotin identification (PhastID) and detail the insulin-stimulated changes in Rheb-proximity protein networks that were identified using PhastID.

ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader.

Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability. The telomeric repeat-containing RNA (TERRA) that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop. In tumor cells, R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres (ALT) pathway.

ChArmTelo Enables Large-Scale Chromosome Arm-Level Telomere Analysis across Human Populations and in Cancer Patients.

Telomeres are structures protecting chromosome ends. However, a scalable and cost-effective method to investigate chromosome arm-level (ChArm) telomeres (Telos) in large-scale projects is still lacking, hindering intensive investigation of high-resolution telomeres across cancers and other diseases. Here, ChArmTelo, the first computational toolbox to analyze telomeres at chromosome arm level in human and other animal species, using 10X linked-read and similar technologies, is presented.

Multiomics analyses reveal pathological mechanisms of HBV infection and integration in liver cancer.

Hepatitis B virus (HBV) infection and integration are important for hepatocellular carcinoma (HCC) initiation and progression, while disease mechanisms are still largely elusive. Here, we combined bulk and single-cell sequencing technologies to tackle the disease mechanisms of HBV-related HCC. We observed high HBV mutation rate and diversity only in tumors without HBV integration.

A Comprehensive Pan-Cancer Analysis of the Potential Biological Functions and Prognosis Values of RICTOR.

The importance of the network defined by phosphatidylinositol-3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine Kinase (RTK) has been recognized for many years. However, the central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway has only recently come to light. The function of RICTOR in pan-cancer still needs to be systematically elucidated.

Transmembrane nuclease NUMEN/ENDOD1 regulates DNA repair pathway choice at the nuclear periphery.

Proper repair of DNA damage lesions is essential to maintaining genome integrity and preventing the development of human diseases, including cancer. Increasing evidence suggests the importance of the nuclear envelope in the spatial regulation of DNA repair, although the mechanisms of such regulatory processes remain poorly defined. Through a genome-wide synthetic viability screen for PARP-inhibitor resistance using an inducible CRISPR-Cas9 platform and BRCA1-deficient breast cancer cells, we identified a transmembrane nuclease (renamed NUMEN) that could facilitate compartmentalized and non-homologous end joining-dependent repair of double-stranded DNA breaks at the nuclear periphery.

Histone mRNA polyadenylation-mediated inflammation underlies various virus infections and cancers.

The mechanistic understanding of virus infection and inflammation in many diseases is incomplete. Normally, messenger RNA (mRNA) tails of replication-dependent histones (RDH) that safeguard naked nuclear DNAs are protected by a specialized stem-loop instead of polyadenylation. Here, we showed that infection by various RNA viruses (including severe acute respiratory syndrome coronavirus 2) induced aberrant polyadenylation of RDH mRNAs (pARDH) that resulted in inflammation or cellular senescence, based on which we constructed a pARDH inflammation score (pARIS).

Comprehensive RNA-Seq Analysis Pipeline for Non-Model Organisms and Its Application in .

RNA sequencing (RNA-seq) is a high-throughput technology that provides in-depth information on transcriptome. The advancement and dropping costs of RNA sequencing, accompanied by more available reference genomes for different species, make transcriptome analysis in non-model organisms possible. Current obstacles in analyzing RNA-seq data include a lack of functional annotation, which may complicate the process of linking genes to corresponding functions.

Deep-learning model AIBISI predicts bacterial infection across cancer types based on pathological images.

Microorganisms play an important role in many physiological functions. Many studies have found that bacteria also regulate cancer susceptibility and tumor progression by affecting some metabolic or immune system signaling pathways. However, current bacterial detection methods are inaccurate or inefficient.

Biomarkers of aging.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need.

Three-dimensional and single-cell sequencing of liver cancer reveals comprehensive host-virus interactions in HBV infection.

Backgrounds: Hepatitis B virus (HBV) infection is a major risk factor for chronic liver diseases and liver cancer (mainly hepatocellular carcinoma, HCC), while the underlying mechanisms and host-virus interactions are still largely elusive.

Methods: We applied HiC sequencing to HepG2 (HBV-) and HepG2-2.2.

Crotonylation of GAPDH regulates human embryonic stem cell endodermal lineage differentiation and metabolic switch.

Background: Post-translational modifications of proteins are crucial to the regulation of their activity and function. As a newly discovered acylation modification, crotonylation of non-histone proteins remains largely unexplored, particularly in human embryonic stem cells (hESCs).

Methods: We investigated the role of crotonylation in hESC differentiation by introduce crotonate into the culture medium of GFP tagged LTR7 primed H9 cell and extended pluripotent stem cell lines.

Pan-cancer investigation of C-to-U editing reveals its important role in cancer development and new targets for cancer treatment.

RNA editing is prevalent in the transcriptome and is important for multiple cellular processes. C-to-U RNA editing sites (RES) are relatively rare and understudied in humans, compared to A-to-I editing. However, the functional impact of C-to-U editing in human cancers also remains elusive.

mTORC1-Induced Bone Marrow-Derived Mesenchymal Stem Cell Exhaustion Contributes to the Bone Abnormalities in -Deficient Mice of Premature Aging.

Stem cell exhaustion is a hallmark of aging. -deficient mice ( mice) is a murine model that mimics human aging with significant bone abnormalities. The aim of this study is using mice to investigate the functional change of bone marrow-derived mesenchymal stem cells (BMSCs) and explore the underlying mechanism.

CRISPR-assisted transcription activation by phase-separation proteins.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency.

Distinct dosage compensations of ploidy-sensitive and -insensitive X chromosome genes during development and in diseases.

The active X chromosome in mammals is upregulated to balance its dosage to autosomes during evolution. However, it is elusive why the known dosage compensation machinery showed uneven and small influence on X genes. Here, based on >20,000 transcriptomes, we identified two X gene groups (ploidy-sensitive [PSX] and ploidy-insensitive [PIX]), showing distinct but evolutionarily conserved dosage compensations (termed XAR).

Identification and Analysis of Small Molecule Inhibitors of CRISPR-Cas9 in Human Cells.

Genome editing tools based on CRISPR-Cas systems can repair genetic mutations in situ; however, off-target effects and DNA damage lesions that result from genome editing remain major roadblocks to its full clinical implementation. Protein and chemical inhibitors of CRISPR-Cas systems may reduce off-target effects and DNA damage. Here we describe the identification of several lead chemical inhibitors that could specifically inhibit the activity of Cas9 (SpCas9).

Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy.

In addition to investigating the virology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovering the host-virus dependencies are essential to identify and design effective antiviral therapy strategy. Here, we report that the SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) and provide evidence indicating that prevention of ACE2 SUMOylation can block SARS-CoV-2 infection. E3 SUMO ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation enzyme SENP3 reverses this process.