A single natural RNA modification can destabilize a U•A-T-rich RNA•DNA-DNA triple helix DOI Open Access
Charlotte N. Kunkler, Grace E. Schiefelbein, Nathan J. O'Leary

et al.

RNA, Journal Year: 2022, Volume and Issue: 28(9), P. 1172 - 1184

Published: July 12, 2022

Recent studies suggest noncoding RNAs interact with genomic DNA, forming RNA•DNA-DNA triple helices, as a mechanism to regulate transcription. One way cells could the formation of these helices is through RNA modifications. With over 140 naturally occurring modifications, we hypothesize that some modifications stabilize while others destabilize them. Here, focus on pyrimidine-motif helix composed canonical U•A-T and C•G-C base triples. We employed electrophoretic mobility shift assays microscale thermophoresis examine how 11 different at single position in an affect stability: 5-methylcytidine (m 5 C), 5-methyluridine U or rT), 3-methyluridine 3 U), pseudouridine (Ψ), 4-thiouridine (s 4 N 6 -methyladenosine A), inosine (I), each nucleobase 2′- O -methylation (Nm). Compared unmodified triple, have no significant change stability (Um•A-T), ∼2.5-fold decreases U•A-T, Ψ•A-T, s U•A-T), completely disrupt U•A-T). To identify potential biological examples controlled by modification, searched RMVar, database for mapped single-nucleotide resolution, lncRNAs containing modification within pyrimidine-rich sequence. Using assays, binding DNA-DNA 22-mer segment human lncRNA Al157886.1 was destabilized ∼1.7-fold substitution m C known sites. Therefore, cellular be influenced

Language: Английский

Transcription regulation by long non-coding RNAs: mechanisms and disease relevance DOI
Jorge Ferrer, Nadya Dimitrova

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(5), P. 396 - 415

Published: Jan. 19, 2024

Language: Английский

Citations

91
Targeting and engineering long non-coding RNAs for cancer therapy DOI
Michela Coan, Simon Haefliger,

Samir Ounzain

et al.

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: 25(8), P. 578 - 595

Published: Feb. 29, 2024

Language: Английский

Citations

70
Linking discoveries, mechanisms, and technologies to develop a clearer perspective on plant long noncoding RNAs DOI Creative Commons
Kyle Palos, Liang Yu, Caylyn E Railey

et al.

The Plant Cell, Journal Year: 2023, Volume and Issue: 35(6), P. 1762 - 1786

Published: Feb. 4, 2023

Abstract Long noncoding RNAs (lncRNAs) are a large and diverse class of genes in eukaryotic genomes that contribute to variety regulatory processes. Functionally characterized lncRNAs play critical roles plants, ranging from regulating flowering controlling lateral root formation. However, findings the past decade have revealed thousands present plant transcriptomes, characterization has lagged far behind identification. In this setting, distinguishing function noise is challenging. community been at forefront discovery lncRNA biology, providing many functional mechanistic insights increased our understanding gene class. review, we examine key discoveries made biology over two half decades. We describe how pregenomics era informed efforts identify functionally characterize subsequent provide an overview archetypes into which fit speculate on new avenues research may uncover yet more archetypes. Finally, review discusses challenges facing field some exciting molecular computational approaches help inform comparative analyses.

Language: Английский

Citations

46
LncRNAs: the art of being influential without protein DOI Creative Commons
Lorena Ramírez Gonzales, Suze Blom, Rossana Henriques

et al.

Trends in Plant Science, Journal Year: 2024, Volume and Issue: 29(7), P. 770 - 785

Published: Feb. 16, 2024

The plant long noncoding (lnc)RNA field is on the brink of transitioning from large-scale identification lncRNAs to their functional characterization. Due cross-kingdom conservation interaction types and molecular functions, there much be learned mammalian lncRNA research. Here, we discuss different processes involving regulation chromatin splicing. Furthermore, interactome, which includes proteins, other RNAs, DNA. We explore how functionalities could reflected in similar pathways plants hypothesize that several breakthroughs research lead discovery novel functions. Expanding our knowledge biological role multiple applications paves way for future agricultural applications.

Language: Английский

Citations

17
METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling DOI Creative Commons
Jianxing Yin, Fangshu Ding, Zhangchun Cheng

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 12, 2023

Abstract Long noncoding RNAs (lncRNAs) are involved in glioma initiation and progression. Glioma stem cells (GSCs) essential for tumor initiation, maintenance, therapeutic resistance. However, the biological functions underlying mechanisms of lncRNAs GSCs remain poorly understood. Here, we identified that LINC00839 was overexpressed GSCs. A high level associated with GBM progression radiation METTL3-mediated m6A modification on enhanced its expression a YTHDF2-dependent manner. Mechanistically, functioned as scaffold promoting c-Src-mediated phosphorylation β-catenin, thereby inducing Wnt/β-catenin activation. Combinational use celecoxib, an inhibitor signaling, greatly sensitized to radiation. Taken together, our results showed LINC00839, modified by m6A, exerts resistance activating signaling.

Language: Английский

Citations

31
The lncRNA SNHG26 drives the inflammatory-to-proliferative state transition of keratinocyte progenitor cells during wound healing DOI Creative Commons
Dongqing Li, Zhuang Liu, Letian Zhang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 5, 2024

Abstract The cell transition from an inflammatory phase to a subsequent proliferative is crucial for wound healing, yet the driving mechanism remains unclear. By profiling lncRNA expression changes during human skin healing and screening functions, we identify SNHG26 as pivotal regulator in keratinocyte progenitors underpinning this transition. Snhg26 -deficient mice exhibit impaired repair characterized by delayed re-epithelization accompanied exacerbated inflammation. Single-cell transcriptome analysis combined with gain-of-function loss-of-function of vitro ex vivo reveals its specific role facilitating inflammatory-to-proliferative state progenitors. A mechanistic study unravels that interacts relocates transcription factor ILF2 genomic loci, such JUN, IL6, IL8 , CCL20 locus LAMB3 . Collectively, our findings suggest lncRNAs play cardinal roles expediting tissue regeneration may constitute invaluable reservoir therapeutic targets reparative medicine.

Language: Английский

Citations

10
Non-coding RNAs and epithelial mesenchymal transition in cancer: molecular mechanisms and clinical implications DOI Creative Commons
Hashem Khanbabaei, Saeedeh Ebrahimi, Juan L. García-Rodríguez

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Sept. 16, 2022

Abstract Epithelial-mesenchymal transition (EMT) is a fundamental process for embryonic development during which epithelial cells acquire mesenchymal characteristics, and the underlying mechanisms confer malignant features to carcinoma such as dissemination throughout organism resistance anticancer treatments. During past decades, an entire class of molecules, called non-coding RNA (ncRNA), has been characterized key regulator almost every cellular process, including EMT. Like protein-coding genes, ncRNAs can be deregulated in cancer, acting oncogenes or tumor suppressors. The various forms ncRNAs, microRNAs, PIWI-interacting RNAs, small nucleolar transfer RNA-derived fragments, long circular RNAs orchestrate complex regulatory networks EMT at multiple levels. Understanding molecular mechanism provide insights into cancer metastasis may lead novel therapeutic approaches. In this review, we describe recent advances understanding overview ncRNA applications clinic.

Language: Английский

Citations

38
Long noncoding RNAs in cardiovascular disease DOI Creative Commons

Alexander Kohlmaier,

Lesca M. Holdt, Daniel Teupser

et al.

Current Opinion in Cardiology, Journal Year: 2023, Volume and Issue: unknown

Published: March 14, 2023

Purpose of review Here, we recent findings on the role long noncoding RNAs (lncRNAs) in cardiovascular disease (CVD). In addition, highlight some latest lncRNA biology, providing an outlook for future avenues research CVD. Recent publications provide translational evidence from patient studies and animal models specific lncRNAs The molecular effector mechanisms these are diverse. Overall, cell-type selective modulation gene expression is largest common denominator. New methods, such as single-cell profiling CRISPR/Cas9-screening, reveal additional novel mechanistic principles: For example, many establish RNA-based spatial compartments that concentrate proteins. Also, RNA modifications splicing features can be determinants function. Summary passing stage enumerating or recording simplified on-off switches. Mechanistic analyses starting to overarching principles how Exploring with decisive genetic testing vivo remains ultimate test discern loci, by motifs DNA elements, affect CVD pathophysiology.

Language: Английский

Citations

17
Target‐directed microRNA degradation: Mechanisms, significance, and functional implications DOI
Nicholas M. Hiers, Tianqi Li, Conner M. Traugot

et al.

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2024, Volume and Issue: 15(2)

Published: March 1, 2024

Abstract MicroRNAs (miRNAs) are small non‐coding RNAs that play a fundamental role in enabling miRNA‐mediated target repression, post‐transcriptional gene regulatory mechanism preserved across metazoans. Loss of certain animal miRNA genes can lead to developmental abnormalities, disease, and various degrees embryonic lethality. These short normally guide Argonaute (AGO) proteins RNAs, which turn translationally repressed destabilized, silencing the fine‐tune expression maintain cellular homeostasis. Delineating decay has been thoroughly examined thousands studies, yet despite these exhaustive comparatively less is known about how why miRNAs directed for decay. Several key observations over years have noted instances rapid turnover, suggesting endogenous means animals induce degradation. Recently, it was revealed targets, so‐called target‐directed degradation (TDMD) triggers, “trigger” through inducing proteolysis AGO thereby bound miRNA. This process mediated via ZSWIM8 ubiquitin ligase complex, recruited during engagement with triggers. Since its discovery, several studies identified TDMD indispensable proper development. Given expansion this field study, here, we summarize findings led followed discovery ZSWIM8‐dependent TDMD. article categorized under: Regulatory RNAs/RNAi/Riboswitches > RNA Turnover Surveillance Turnover/Surveillance Mechanisms Disease Development

Language: Английский

Citations

8
The emerging landscape of non-conventional RNA functions in atherosclerosis DOI Open Access
Floriana Maria Farina, Christian Weber, Donato Santovito

et al.

Atherosclerosis, Journal Year: 2023, Volume and Issue: 374, P. 74 - 86

Published: Jan. 20, 2023

Language: Английский

Citations

16