Role of long noncoding RNAs in diabetes-associated peripheral arterial disease DOI Creative Commons
Alonso Tapia, Xuejing Liu, Naseeb Kaur Malhi

et al.

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: July 24, 2024

Abstract Diabetes mellitus (DM) is a metabolic disease that heightens the risks of many vascular complications, including peripheral arterial (PAD). Various types cells, but not limited to endothelial cells (ECs), smooth muscle (VSMCs), and macrophages (MΦs), play crucial roles in pathogenesis DM-PAD. Long non-coding RNAs (lncRNAs) are epigenetic regulators important cellular function, their dysregulation DM can contribute PAD. This review focuses on developing field lncRNAs emerging linking We studies investigating role processes contributing DM-PAD, those ECs, VSMCs, MΦ. By examining intricate molecular landscape governed by these relevant cell types, we hope shed light EC dysfunction, inflammatory responses, remodeling Additionally, provide an overview research approach methodologies, from identifying disease-relevant characterizing functions context also discuss potential leveraging diagnosis therapeutics for Collectively, this provides summary lncRNA-regulated DM-PAD highlights translational lncRNA biology tackle increasingly prevalent complex disease. Graphical

Language: Английский

Amplifying gene expression with RNA-targeted therapeutics DOI Open Access
Olga Khorkova, Jack Stahl,

Aswathy Joji

et al.

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(7), P. 539 - 561

Published: May 30, 2023

Language: Английский

Citations

69
Identification of RNA structures and their roles in RNA functions DOI
Xinang Cao, Yueying Zhang, Yiliang Ding

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(10), P. 784 - 801

Published: June 26, 2024

Language: Английский

Citations

14
COVID and the brain: researchers zero in on how damage occurs DOI Open Access
Michael S. Marshall

Nature, Journal Year: 2021, Volume and Issue: 595(7868), P. 484 - 485

Published: July 7, 2021

Language: Английский

Citations

46
LNCing RNA to immunity DOI Creative Commons
Daniel Peltier,

Alexis Roberts,

Pavan Reddy

et al.

Trends in Immunology, Journal Year: 2022, Volume and Issue: 43(6), P. 478 - 495

Published: April 29, 2022

Language: Английский

Citations

25
Long non-coding RNA-targeting therapeutics: discovery and development update DOI
Olga Khorkova, Jack Stahl,

Aswathy Joji

et al.

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 18(9), P. 1011 - 1029

Published: July 19, 2023

Introduction lncRNAs are major players in regulatory networks orchestrating multiple cellular functions, such as 3D chromosomal interactions, epigenetic modifications, gene expression and others. Due to progress the development of nucleic acid-based therapeutics, potentially represent easily accessible therapeutic targets.Areas covered Currently, significant efforts directed at studies that can tap enormous potential lncRNAs. This review describes recent developments this field, particularly focusing on clinical applications.Expert opinion Extensive druggable target range lncRNA combined with high specificity accelerated process therapeutics open new prospects for treatment areas extreme unmet medical need, genetic diseases, aggressive cancers, protein deficiencies, subsets common diseases caused by known mutations. Although currently wide acceptance lncRNA-targeting is impeded need parenteral or direct-to-CNS administration, less invasive techniques orally available/BBB-penetrant showing early successes. Recently, mRNA-based COVID-19 vaccines have demonstrated safety all aspects technology, including chemical modifications acids nanoparticle delivery. These trends position drugs future drug development, especially area personalized medicine.

Language: Английский

Citations

15
RNA exosome drives early B cell development via noncoding RNA processing mechanisms DOI
Brice Laffleur,

Carolina R. Batista,

Wanwei Zhang

et al.

Science Immunology, Journal Year: 2022, Volume and Issue: 7(72)

Published: June 3, 2022

B cell development is linked to successful V(D)J recombination, allowing receptor expression and ultimately antibody secretion for adaptive immunity. Germline noncoding RNAs (ncRNAs) are produced at immunoglobulin (Ig) loci during but their function posttranscriptional regulation incompletely understood. Patients with trichohepatoenteric syndrome, characterized by RNA exosome pathway component mutations, exhibit lymphopenia, thus demonstrating the importance of ncRNA surveillance in humans. To understand role early greater detail, we generated mouse models harboring a cell–specific cre allele ( Mb1 ), coupled conditional inversion-deletion alleles one core Exosc3 ) or RNase catalytic subunits Exosc10 Dis3 ). We noticed increased whereas developmental blockade pro–B stage was observed different knockout mice, overlapping lack productive rearrangements VDJ genes Ig heavy chain Igh This unsuccessful recombination prevented differentiation into pre–B cells, accumulation ncRNAs up-regulation p53 pathway. Introduction prearranged partly rescued population -deficient although V-J defects were light kappa κ), preventing subsequent development. These observations demonstrated that complex important κ establish relevance processing optimal diversification these

Language: Английский

Citations

19
Regulation of the epigenome through RNA modifications DOI

Emmely A. Patrasso,

Sweta Raikundalia, Daniel Arango

et al.

Chromosoma, Journal Year: 2023, Volume and Issue: 132(3), P. 231 - 246

Published: May 4, 2023

Language: Английский

Citations

11
RBM22 regulates RNA polymerase II 5′ pausing, elongation rate, and termination by coordinating 7SK-P-TEFb complex and SPT5 DOI Creative Commons
Xian Du, Wenying Qin, Chunyu Yang

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: April 19, 2024

Abstract Background Splicing factors are vital for the regulation of RNA splicing, but some have also been implicated in regulating transcription. The underlying molecular mechanisms their involvement transcriptional processes remain poorly understood. Results Here, we describe a direct role splicing factor RBM22 coordinating multiple steps Polymerase II (RNAPII) transcription human cells. protein widely occupies RNAPII-transcribed gene locus nucleus. Loss promotes RNAPII pause release, reduces elongation velocity, and provokes readthrough genome-wide, coupled with production transcripts containing sequences from downstream gene. preferentially binds to hyperphosphorylated, transcriptionally engaged coordinates its dynamics by homeostasis 7SK-P-TEFb complex association between SPT5 at chromatin level. Conclusions Our results uncover multifaceted orchestrating program provide evidence implicating both kinetics termination control.

Language: Английский

Citations

4
An RNA-centric view of transcription and genome organization DOI
Jonathan E. Henninger, Richard A. Young

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(19), P. 3627 - 3643

Published: Oct. 1, 2024

Language: Английский

Citations

4
Rewired m6A methylation of promoter antisense RNAs in Alzheimer disease regulates global gene transcription in the 3D nucleome DOI Creative Commons

Benxia Hu,

Yuqiang Shi,

Feng Xiong

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 23, 2025

Abstract N 6 -methyladenosine (m6A) is the most prevalent internal RNA modification that can impact mRNA expression post-transcriptionally. Recent progress indicates m6A also acts on nuclear or chromatin-associated RNAs to transcriptional and epigenetic processes. However, landscapes functional roles of in human brains neurodegenerative diseases, including Alzheimer’s disease (AD), have been under-explored. Here, we examined methylome using total RNA-seq meRIP-seq middle frontal cortex tissues post-mortem from individuals with AD age-matched counterparts. Our results revealed AD-associated alteration methylation both mRNAs various noncoding RNAs. Notably, a series p romoter ntisense (paRNAs) displayed cell-type-specific changes AD, one produced adjacent MAPT locus encodes Tau protein. We found MAPT-paRNA enriched neurons, positively controls its expression. In iPSC-derived excitatory promotes hundreds genes related neuronal synaptic functions, key resilience gene MEF2C , plays neuroprotective role against excitotoxicity. By examining RNA-DNA interactome three-dimensional (3D) nuclei brains, demonstrated brain paRNAs interact cis - trans -chromosomal target their transcription. These data together reveal previously unexplored functions regulation, survival pathogenesis.

Language: Английский

Citations

0