Cryo-EM reveals mechanisms of natural RNA multivalency.

Homo-oligomerization of biological macromolecules leads to functional assemblies that are critical to understanding various cellular processes. However, RNA quaternary structures have been rarely reported. Comparative genomics analysis has identified RNA families containing hundreds of sequences that adopt conserved secondary structures and likely fold into complex three-dimensional (3D) structures.

Structures and membrane interactions of human OAT1 in complex with clinical used drugs.

Organic anion transporters (OATs) in mammals mediate the renal excretion of numerous structurally diverse organic anionic compounds. Therapeutically inhibiting OATs has emerged as a strategy to modulate the elimination or retention of these substrates. Among them, OAT1 plays a pivotal role in the pharmacokinetics and drug-drug interactions of a wide range of prescription medications.

Complex structure and activation mechanism of arginine kinase McsB by McsA.

Protein phosphorylation is a pivotal post-translational modification modulating various cellular processes. In Gram-positive bacteria, the protein arginine kinase McsB, along with its activator McsA, has a key role in labeling misfolded and damaged proteins during stress. However, the activation mechanism of McsB by McsA remains elusive.

mA modification of lipoyltransferase 1 inhibits bladder cancer progression by activating cuproptosis.

Cuproptosis, a cell death process caused by copper ions, is mediated by protein lipidation related to lipoic acid metabolism. There is a close connection between cuproptosis and the progression and prognosis of various tumors. Here, we identified lipoyltransferase 1 (LIPT1), a key gene related to cuproptosis, was downregulated in bladder cancer (BLCA) and was associated with unfavorable patient prognosis.

m6A-Mediated Induction of 7-Dehydrocholesterol Reductase Stimulates Cholesterol Synthesis and cAMP Signaling to Promote Bladder Cancer Metastasis.

Dysregulation of cholesterol homeostasis occurs in multiple types of tumors and promotes cancer progression. Investigating the specific processes that induce abnormal cholesterol metabolism could identify therapeutic targets to improve cancer treatment. In this investigation, we observed upregulation of 7-dehydrocholesterol reductase (DHCR7), a vital enzyme involved in the synthesis of cholesterol, within bladder cancer tissues in comparison to normal tissues, which was correlated with increased bladder cancer metastasis.

Cellular senescence and metabolic reprogramming model based on bulk/single-cell RNA sequencing reveals PTGER4 as a therapeutic target for ccRCC.

Clear cell renal cell carcinoma (ccRCC) is the prevailing histological subtype of renal cell carcinoma and has unique metabolic reprogramming during its occurrence and development. Cell senescence is one of the newly identified tumor characteristics. However, there is a dearth of methodical and all-encompassing investigations regarding the correlation between the broad-ranging alterations in metabolic processes associated with aging and ccRCC.

Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer.

Bladder cancer (BLCA) is the most frequent malignant tumor of the genitourinary system. Postoperative chemotherapy drug perfusion and chemotherapy are important means for the treatment of BLCA. However, once drug resistance occurs, BLCA develops rapidly after recurrence.

Pseudomonas aeruginosa regulator PvrA binds simultaneously to multiple pseudo-palindromic sites for efficient transcription activation.

Tetracycline repressor (TetR) family regulators (TFRs) are the largest group of DNA-binding transcription factors and are widely distributed in bacteria and archaea. TFRs play vital roles in controlling the expression of various genes and regulating diverse physiological processes. Recently, a TFR protein Pseudomonas virulence regulator A (PvrA), was identified from Pseudomonas aeruginosa as the transcriptional activator of genes involved in fatty acid utilization and bacterial virulence.

Fatty Acid Oxidation Mediated by Malonyl-CoA Decarboxylase Represses Renal Cell Carcinoma Progression.

Unlabelled: Fatty acid metabolism reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Increased lipid storage supports ccRCC progression, highlighting the importance of understanding the molecular mechanisms driving altered fatty acid synthesis in tumors. Here, we identified that malonyl-CoA decarboxylase (MLYCD), a key regulator of fatty acid anabolism, was downregulated in ccRCC, and low expression correlated with poor prognosis in patients.

DnaQ mediates directional spacer acquisition in the CRISPR-Cas system by a time-dependent mechanism.

In the spacer acquisition stage of CRISPR-Cas immunity, spacer orientation and protospacer adjacent motif (PAM) removal are two prerequisites for functional spacer integration. Cas4 has been implicated in both processing the prespacer and determining the spacer orientation. In Cas4-lacking systems, host 3'-5' DnaQ family exonucleases were recently reported to play a Cas4-like role.

Cryo-EM structure of the nucleocapsid-like assembly of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a nonsegmented, negative strand RNA virus that has caused severe lower respiratory tract infections of high mortality rates in infants and the elderly, yet no effective vaccine or antiviral therapy is available. The RSV genome encodes the nucleoprotein (N) that forms helical assembly to encapsulate and protect the RNA genome from degradation, and to serve as a template for transcription and replication. Previous crystal structure revealed a decameric ring architecture of N in complex with the cellular RNA (N-RNA) of 70 nucleotides (70-nt), whereas cryo-ET reconstruction revealed a low-resolution left-handed filament, in which the crystal monomer structure was docked with the helical symmetry applied to simulate a nucleocapsid-like assembly of RSV.

Modular characterization of SARS-CoV-2 nucleocapsid protein domain functions in nucleocapsid-like assembly.

SARS-CoV-2 and its variants, with the Omicron subvariant XBB currently prevailing the global infections, continue to pose threats on public health worldwide. This non-segmented positive-stranded RNA virus encodes the multi-functional nucleocapsid protein (N) that plays key roles in viral infection, replication, genome packaging and budding. N protein consists of two structural domains, NTD and CTD, and three intrinsically disordered regions (IDRs) including the N, the serine/arginine rich motif (SR), and the C.

Cryo-EM structure of a eukaryotic zinc transporter at a low pH suggests its Zn-releasing mechanism.

Zinc transporter 8 (ZnT8) is mainly expressed in pancreatic islet β cells and is responsible for H-coupled uptake (antiport) of Zn into the lumen of insulin secretory granules. Structures of human ZnT8 and its prokaryotic homolog YiiP have provided structural basis for constructing a plausible transport cycle for Zn. However, the mechanistic role that protons play in the transport process remains unclear.

A Metabolism-Related Gene Landscape Predicts Prostate Cancer Recurrence and Treatment Response.

Background: Prostate cancer (PCa) is the most common malignant tumor in men. Although clinical treatments of PCa have made great progress in recent decades, once tolerance to treatments occurs, the disease progresses rapidly after recurrence. PCa exhibits a unique metabolic rewriting that changes from initial neoplasia to advanced neoplasia.

DNA nanostructures directed by RNA clamps.

DNA chains can be folded rationally by using DNA staples, and the programmed structures are of great potential in nanomaterial studies. However, due to the short DNA staples forming duplexes and displaying limitations in structural diversity and stability, the folded DNA nanostructures are usually generated with structural mis-formations, low yields and poor efficiencies, which can restrict their folding patterns and applications. To overcome these problems, we set out to use RNA as a clamp to form polygons, and herein demonstrated the ability to use a structural RNA-but not its corresponding DNA-to fold DNA chains into nanostructures with high efficiency (up to a 95.