Research progress of RNA modification and its association with human diseases DOI Open Access
Chun‐Chun Gao, Min‐Xin Guan,

He Xiao

et al.

Scientia Sinica Vitae, Journal Year: 2023, Volume and Issue: 53(11), P. 1502 - 1526

Published: Aug. 10, 2023

Post-transcriptional chemical modifications are prevalent in various RNA molecules and play a profound role biological functions, including the regulation of splicing, translation, transport, localization, stability. Recent advancements high-throughput sequencing modification detection technologies have facilitated significant breakthroughs accurately identifying localizing different modifications, such as m6A, m5C, m1A. As novel category epigenetic transcriptional biomarkers, garnered considerable attention diagnosis treatment numerous diseases, tumors, neurological diseases immunological diseases. This review aims to provide comprehensive overview roles editing, underlying molecular mechanisms regulating protein expression further highlight progress application disease treatment.

Language: Английский

Quantitative Contributions of Hepatic and Renal Organic Cation Transporters to the Clinical Pharmacokinetic Cimetidine–Metformin Interaction DOI

Anoud Ailabouni,

Dilip Kumar Singh, Aarzoo Thakur

et al.

Clinical Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

The widely prescribed oral anti‐diabetic drug metformin is eliminated unchanged in the urine primarily through active tubular secretion. This process mediated by organic cation transporter 2 (OCT2), an uptake expressed on basolateral membrane of renal proximal tubule cells. Metformin into liver, site action, 1 (OCT1), which sinusoidal hepatocytes. Sixteen healthy adults participated a clinical pharmacokinetic drug–drug interaction study they were orally administered (50 mg) as dual OCT1/2 substrate alone (baseline) and with cimetidine (400 OCT inhibitor. Relative to baseline, systemic plasma exposure increased 24% ( p < 0.05) presence cimetidine, was accompanied disproportional decrease (8%) clearance = 0.005). Genetic variants OCT1 OCT2 moderately impacted significance magnitude interaction. Collectively, we hypothesized that cimetidine–metformin involves inhibition hepatic well OCT2. We tested this hypothesis developing physiologically based (PBPK) model assessing potential biomarkers gain mechanistic insight transporters involved PBPK predicted inhibits and, lesser extent, following supports minimal role for

Language: Английский

Citations

1
Epigenetic modifications of DNA and RNA in Alzheimer’s disease DOI Creative Commons
Paula Martínez-Feduchi, Peng Jin, Bing Yao

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: April 25, 2024

Alzheimer’s disease (AD) is a complex neurodegenerative disorder and the most common form of dementia. There are two main types AD: familial sporadic. Familial AD linked to mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), presenilin-2 (PSEN2). On other hand, sporadic more has genetic, epigenetic, environmental components that influence onset progression. Investigating epigenetic mechanisms associated with essential for increasing understanding pathology identifying biomarkers diagnosis treatment. Chemical covalent modifications on DNA RNA can epigenetically regulate gene expression at transcriptional post-transcriptional levels play protective or pathological roles diseases.

Language: Английский

Citations

7
Plant RNA-binding proteins: Phase separation dynamics and functional mechanisms underlying plant development and stress responses DOI Creative Commons

Sheng Fan,

Yu Zhang,

Shaobo Zhu

et al.

Molecular Plant, Journal Year: 2024, Volume and Issue: 17(4), P. 531 - 551

Published: Feb. 27, 2024

RNA-binding proteins (RBPs) accompany RNA from synthesis to decay, mediating every aspect of metabolism and impacting diverse cellular developmental processes in eukaryotes. Many RBPs undergo phase separation along with their bound form function dynamic membraneless biomolecular condensates for spatiotemporal coordination or regulation metabolism. Increasing evidence suggests that phase-separating domains intrinsically disordered regions play important roles plant development stress adaptation. Here, we summarize the current knowledge about how partitioning into controls enables sensing experimental changes confer growth plasticity under conditions, a focus on dynamics functional mechanisms RBP-rich nuclear cytoplasmic granules We also discuss multiple factors, such as environmental signals, protein modifications, N

Language: Английский

Citations

6
Metabolic Reprogramming in Response to Freund’s Adjuvants: Insights from Serum Metabolomics DOI Creative Commons
Kiruthiga Mone, Edgardo José García,

Fatema Abdullatif

et al.

Microorganisms, Journal Year: 2025, Volume and Issue: 13(3), P. 492 - 492

Published: Feb. 22, 2025

Freund’s adjuvants have been used in vaccine and autoimmune settings, their effects can be overlapping or unique to each. While both incomplete (IFA) complete (CFA) influence antibody T cell responses, the robust helper 1 cytokines induced by mycobacterial components make CFA powerful immunostimulating adjuvant. In these studies, adjuvant are investigated a select population of cells, changes, if any, with metabolic alterations systemic compartment unclear. We whether IFA influenced shifts mice immunized saline, IFA, using Mycobacterium tuberculosis var. bovis Bacillus Calmette–Guérin (BCG) as positive control. After seven days immunization, we analyzed serum metabolite profiles liquid chromatography coupled high-resolution mass spectrometry multivariate statistical analysis identify features between groups. The data revealed that, scores space, BCG groups were more closely aligned compared saline group, while group displayed an intermediate profile. Furthermore, comparisons showed significant perturbations lipid amino acid metabolism, particularly involving glycerophospholipids, cysteine, aromatic acids. contrast, indicated pronounced disruption central energy metabolism pathways, such citric cycle pyruvate metabolism. Together, suggest that response might play role modulating immune responses.

Language: Английский

Citations

0
The functions and modifications of tRNA-derived small RNAs in cancer biology DOI
Aly M A Saad, Kun Zhang,

Qianqian Deng

et al.

Cancer and Metastasis Reviews, Journal Year: 2025, Volume and Issue: 44(1)

Published: March 1, 2025

Language: Английский

Citations

0
The secret life of N1-methyladenosine: a review on its regulatory functions DOI
Nathalie Nguyen, Xi-Sheng Liu, Anindya Dutta

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169099 - 169099

Published: March 1, 2025

Language: Английский

Citations

0
Identification and Characterization of the RNA Modifying Factors PUS7 and WTAP as Key Components for the Control of Tumor Biological Processes in Renal Cell Carcinomas DOI Creative Commons
Tim Hohmann, Urszula Grabiec,

Faramarz Dehghani

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 266 - 266

Published: April 9, 2025

Current research discusses the putative importance of RNA modification in tumor diseases. These modifications include predominantly pseudouridinylation, ortho-methylations on ribose residues, as well methylations organic bases. Such chemical directly influence fundamental properties such transcript stability, alternative splicing, and translation efficiency, all which are basic requirements for (tumor) cell proliferation, metabolism, migration, apoptosis resistance, etc. In this comparative study, two RNA-modifying factors, pseudouridine synthase 7 (PUS7, pseudouridinylation) WT1-associated protein (WTAP, m6A methylation), were identified using data from human renal carcinoma (RCC) tumors. PUS7 WTAP showed a statistically significant correlation with relevant proliferation prognosis markers CXCR4, TP53, PTEN, NRAS, immune checkpoints HLA-G LGALS9 associated effect overall survival. Furthermore, analyses also further target mRNAs biology WTAP. particular, components direct relevance mitosis, cycle, division, WNT pathway, identified.

Language: Английский

Citations

0
Advancing mRNA vaccines for infectious diseases: key components, innovations, and clinical progress DOI Creative Commons

Sha Li,

Lu Hai Zheng, Jianhui Zhong

et al.

Essays in Biochemistry, Journal Year: 2025, Volume and Issue: 69(02)

Published: May 1, 2025

Vaccination remains a cornerstone in preventing infectious diseases and managing outbreaks. The COVID-19 pandemic has underscored the revolutionary impact of mRNA vaccine technology, which utilizes pathogenderived genomic sequences to generate specific antigens. This process involves vitro transcription mRNA, encoding target antigens that are subsequently encapsulated within lipid nanoparticles (LNPs) for efficient delivery into host cells. Once internalized, enables antigen expression, triggering robust immune response. platform dramatically accelerates development timelines offers unparalleled adaptability, making vaccines particularly advantageous addressing emerging diseases. clinical success BNT162b2 (Pfizer-BioNTech) mRNA-1273 (Moderna) fueled broader applications, including influenza, respiratory syncytial virus (RSV), Zika, HIV. Notably, mRNA-1345 became first FDA-approved RSV vaccine, while self-amplifying RNA multivalent advancing trials. However, CureVac’s CVnCoV failed due lack nucleoside modifications, mRNA-1325 (Zika) showed poor immunogenicity. Additionally, mRNA-1365 (RSV) faced an FDA hold safety concerns. These cases highlight need continued optimization sequence design, delivery, assessment. Despite advancements, key hurdle persists, instability, ultra-low storage requirements, LNP liver accumulation. Innovations such as lyophilization selective organ targeting technology being explored improve stability extrahepatic delivery. review examines strategies, progress, challenges, providing insights future developments this evolving field.

Language: Английский

Citations

0
Chemical and Enzyme‐Mediated Chemical Reactions for Studying Nucleic Acids and Their Modifications DOI

Tengwei Li,

Chongguang Cheng,

Jianzhao Liu

et al.

ChemBioChem, Journal Year: 2024, Volume and Issue: 25(15)

Published: May 14, 2024

Nucleic acids are genetic information-carrying molecules inside cells. Apart from basic nucleotide building blocks, there exist various naturally occurring chemical modifications on nucleobase and ribose moieties, which greatly increase the encoding complexity of nuclei acids, contribute to alteration nucleic acid structures, play versatile regulation roles in gene expression. To study functions certain biological contexts, robust tools specifically label identify these macromolecules their modifications, illuminate structures highly necessary. In this review, we summarize recent technique advances using enzyme-mediated reactions structures. By highlighting principles techniques, aim present a perspective advancement field as well offer insights into developing specific precise enzyme catalysis utilized for modifications.

Language: Английский

Citations

3
Non‐m6A RNA modifications in haematological malignancies DOI Creative Commons
Meiling Chen, Yuanzhong Chen, Kitty Wang

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(6)

Published: June 1, 2024

Dysregulated RNA modifications, stemming from the aberrant expression and/or malfunction of modification regulators operating through various pathways, play pivotal roles in driving progression haematological malignancies. Among N

Language: Английский

Citations

2