Dietary Enterococcus faecium NCIMB 11181 supplementation mitigates intestinal and systemic inflammation induced by avian pathogenic Escherichia coli O78 infection in broiler chickens.

The development of non-antibiotic agents to control avian colibacillosis has become urgent work. Probiotics Enterococcus faecium strains are promising antibiotic alternatives to combat pathogen infection. This study investigated the protective efficacy and action mechanism of dietary probiotic Enterococcus faecium NCIMB 11181 (E.

Pan-Cancer Analysis of G Protein-Coupled Receptors as Cancer Driver Genes and Drug Repurposing Targets.

G protein-coupled receptors (GPCRs), the largest family of currently approved drug targets, are rarely targeted for cancer therapy. There is limited research on the role of GPCRs in pan-cancer, particularly regarding the underlying causes of their abnormal expression. The abnormal expression of GPCRs in tumors has generally been attributed to mutations and promoter methylation.

The RNA Binding Protein Bcas2 is Required for Antibody Class Switch in Activated-B Cells.

In children, hyper-IgM syndrome type 1 (HIGM1) is a type of severe antibody disorder, the pathogenesis of which remains unclear. The antibody diversity is partially determined by the alternative splicing (AS) in the germline, which is mainly regulated by RNA-binding proteins, including Breast cancer amplified sequence 2 (Bcas2). However, the effect of Bcas2 on AS and antibody production in activated B cells, the main immune cell type in the germline, remains unknown.

Cardiac Slc25a49-Mediated Energy Reprogramming Governs Doxorubicin-Induced Cardiomyopathy through the G6P-AP-1-Sln Axis.

Doxorubicin (Dox), a potent antitumor drug, is linked to cardiac toxicity. Few mechanism-based therapies against cardiotoxicity are available. Dysfunction in mitochondrial energy metabolism contributes to Dox-induced cardiomyopathy.

A read-through circular RNA RCRIN inhibits metabolic dysfunction-associated steatotic liver disease.

Background & Aims: The molecular mechanisms underlying metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive and whether non-coding RNAs can serve as biomarkers and therapeutic targets in MASLD has not been determined.

Methods: Exon capture RNA-sequencing analysis was used to identify read-through circular RNAs (rt-circRNAs) in livers from three patients with MASLD and three controls without MASLD. Hepatocyte-specific deletion or overexpression of rt-circRNA RCRIN were utilized to study MASLD pathogenesis.

BCAS2 and hnRNPH1 orchestrate alternative splicing for DNA double-strand break repair and synapsis in meiotic prophase I.

Understanding the intricacies of homologous recombination during meiosis is crucial for reproductive biology. However, the role of alternative splicing (AS) in DNA double-strand breaks (DSBs) repair and synapsis remains elusive. In this study, we investigated the impact of conditional knockout (cKO) of the splicing factor gene Bcas2 in mouse germ cells, revealing impaired DSBs repair and synapsis, resulting in non-obstructive azoospermia (NOA).

RNA splicing controls organ-wide maturation of postnatal heart in mice.

Postnatal cardiac development requires the orchestrated maturation of diverse cellular components for which unifying control mechanisms are still lacking. Using full-length sequencing, we examined the transcriptomic landscape of the maturating mouse heart (E18.5-P28) at single-cell and transcript isoform resolution.

SARS-CoV-2 RNA stabilizes host mRNAs to elicit immunopathogenesis.

SARS-CoV-2 RNA interacts with host factors to suppress interferon responses and simultaneously induces cytokine release to drive the development of severe coronavirus disease 2019 (COVID-19). However, how SARS-CoV-2 hijacks host RNAs to elicit such imbalanced immune responses remains elusive. Here, we analyzed SARS-CoV-2 RNA in situ structures and interactions in infected cells and patient lung samples using RIC-seq.

Long-range RNA structures in the human transcriptome beyond evolutionarily conserved regions.

RNA structure has been increasingly recognized as a critical player in the biogenesis and turnover of many transcripts classes. In eukaryotes, the prediction of RNA structure by thermodynamic modeling meets fundamental limitations due to the large sizes and complex, discontinuous organization of eukaryotic genes. Signatures of functional RNA structures can be found by detecting compensatory substitutions in homologous sequences, but a comparative approach is applicable only within conserved sequence blocks.

Complementary Alu sequences mediate enhancer-promoter selectivity.

Enhancers determine spatiotemporal gene expression programs by engaging with long-range promoters. However, it remains unknown how enhancers find their cognate promoters. We recently developed a RNA in situ conformation sequencing technology to identify enhancer-promoter connectivity using pairwise interacting enhancer RNAs and promoter-derived noncoding RNAs.

RNA in situ conformation sequencing reveals novel long-range RNA structures with impact on splicing.

Over recent years, long-range RNA structure has emerged as a factor that is fundamental to alternative splicing regulation. An increasing number of human disorders are now being associated with splicing defects; hence it is essential to develop methods that assess long-range RNA structure experimentally. RNA in situ conformation sequencing (RIC-seq) is a method that recapitulates RNA structure within physiological RNA-protein complexes.

NOVA1 prevents overactivation of the unfolded protein response and facilitates chromatin access during human white adipogenesis.

The molecular mechanism underlying white adipogenesis in humans has not been fully elucidated beyond the transcriptional level. Here, we found that the RNA-binding protein NOVA1 is required for the adipogenic differentiation of human mesenchymal stem cells. By thoroughly exploring the interactions between NOVA1 and its binding RNA, we proved that NOVA1 deficiency resulted in the aberrant splicing of DNAJC10 with an in-frame premature stop codon, reduced DNAJC10 expression at the protein level and hyperactivation of the unfolded protein response (UPR).

Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation.

RNA-binding proteins (RBPs) bind at different positions of the pre-mRNA molecules to promote or reduce the usage of a particular exon. Seeking to understand the working principle of these positional effects, we develop a capture RIC-seq (CRIC-seq) method to enrich specific RBP-associated in situ proximal RNA-RNA fragments for deep sequencing. We determine hnRNPA1-, SRSF1-, and PTBP1-associated proximal RNA-RNA contacts and regulatory mechanisms in HeLa cells.

Research Progress of HS Donors Conjugate Drugs Based on ADTOH.

HS is an endogenous gas signaling molecule and its multiple biological effects have been demonstrated. The abnormal level of HS is closely related to the occurrence and development of many diseases, and HS donors has important pharmacological implications. In recent years, HS donors represented by ADTOH (5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione) are often used to synthesize new 'conjugate' compounds that can release HS and parent drugs.

APAF1-Binding Long Noncoding RNA Promotes Tumor Growth and Multidrug Resistance in Gastric Cancer by Blocking Apoptosome Assembly.

Chemotherapeutics remain the first choice for advanced gastric cancers (GCs). However, drug resistance and unavoidable severe toxicity lead to chemotherapy failure and poor prognosis. Long noncoding RNAs (lncRNAs) play critical roles in tumor progression in many cancers, including GC.

Research advances on interferon (IFN) response during BVDV infection.

Bovine viral diarrhea virus (BVDV) is an important pathogen responsible for significant economic loss to cattle. BVDV infection in pregnant cattle leads to fetal infection and reproductive losses, including early embryonic death, abortion, and stillbirth. Importantly, vaccinated heifers could not provide fetal protection against BVDV.

Recent advances in RNA structurome.

RNA structures are essential to support RNA functions and regulation in various biological processes. Recently, a range of novel technologies have been developed to decode genome-wide RNA structures and novel modes of functionality across a wide range of species. In this review, we summarize key strategies for probing the RNA structurome and discuss the pros and cons of representative technologies.

The architecture of the SARS-CoV-2 RNA genome inside virion.

SARS-CoV-2 carries the largest single-stranded RNA genome and is the causal pathogen of the ongoing COVID-19 pandemic. How the SARS-CoV-2 RNA genome is folded in the virion remains unknown. To fill the knowledge gap and facilitate structure-based drug development, we develop a virion RNA in situ conformation sequencing technology, named vRIC-seq, for probing viral RNA genome structure unbiasedly.

Global profiling of RNA-binding protein target sites by LACE-seq.

RNA-binding proteins (RBPs) have essential functions during germline and early embryo development. However, current methods are unable to identify the in vivo targets of a RBP in these low-abundance cells. Here, by coupling RBP-mediated reverse transcription termination with linear amplification of complementary DNA ends and sequencing, we present the LACE-seq method for identifying RBP-regulated RNA networks at or near the single-oocyte level.

Global in situ profiling of RNA-RNA spatial interactions with RIC-seq.

Emerging evidence has demonstrated that RNA-RNA interactions are vital in controlling diverse biological processes, including transcription, RNA splicing and protein translation. RNA in situ conformation sequencing (RIC-seq) is a technique for capturing protein-mediated RNA-RNA proximal interactions globally in living cells at single-base resolution. Cells are first treated with formaldehyde to fix all the protein-mediated RNA-RNA interactions in situ.

Enhancer RNA: biogenesis, function, and regulation.

Enhancers are noncoding DNA elements that are present upstream or downstream of a gene to control its spatial and temporal expression. Specific histone modifications, such as monomethylation on histone H3 lysine 4 (H3K4me1) and H3K27ac, have been widely used to assign enhancer regions in mammalian genomes. In recent years, emerging evidence suggests that active enhancers are bidirectionally transcribed to produce enhancer RNAs (eRNAs).

RIC-seq for global in situ profiling of RNA-RNA spatial interactions.

Highly structured RNA molecules usually interact with each other, and associate with various RNA-binding proteins, to regulate critical biological processes. However, RNA structures and interactions in intact cells remain largely unknown. Here, by coupling proximity ligation mediated by RNA-binding proteins with deep sequencing, we report an RNA in situ conformation sequencing (RIC-seq) technology for the global profiling of intra- and intermolecular RNA-RNA interactions.

The RNA-binding protein ROD1/PTBP3 cotranscriptionally defines AID-loading sites to mediate antibody class switch in mammalian genomes.

Activation-induced cytidine deaminase (AID) mediates class switching by binding to a small fraction of single-stranded DNA (ssDNA) to diversify the antibody repertoire. The precise mechanism for highly selective AID targeting in the genome has remained elusive. Here, we report an RNA-binding protein, ROD1 (also known as PTBP3), that is both required and sufficient to define AID-binding sites genome-wide in activated B cells.

Predicting and Interpreting the Structure of Type IV Pilus of Electricigens by Molecular Dynamics Simulations.

Nanowires that transfer electrons to extracellular acceptors are important in organic matter degradation and nutrient cycling in the environment. Geobacter pili of the group of Type IV pilus are regarded as nanowire-like biological structures. However, determination of the structure of pili remains challenging due to the insolubility of monomers, presence of surface appendages, heterogeneity of the assembly, and low-resolution of electron microscopy techniques.