Coding, or non-coding, that is the question

Cell Research, Journal Year: 2024, Volume and Issue: 34(9), P. 609 - 629

Published: July 25, 2024

The advent of high-throughput sequencing uncovered that our genome is pervasively transcribed into RNAs are seemingly not translated proteins. It was also found non-coding RNA transcripts outnumber canonical protein-coding genes. This mindboggling discovery prompted a surge in research started unraveling the functional relevance these new genetic units, shaking classic definition "gene". While revolution still taking place, polysome/ribosome profiling and mass spectrometry analyses revealed peptides can be from non-canonical open reading frames. Therefore, it becoming evident coding vs dichotomy way blurrier than anticipated. In this review, we focus on several examples which binary classification genes outdated, since same bifunctional gene expresses both products. We discuss implications intricate usage terms molecular mechanisms expression biological outputs, often concordant, but surprisingly discordant. Finally, methodological caveats associated with study genes, highlight opportunities challenges therapeutic exploitation intricacy towards development anticancer therapies.

Language: Английский

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New insights into the physiology and pathophysiology of the atypical sodium leak channel NALCN

Physiological Reviews, Journal Year: 2023, Volume and Issue: 104(1), P. 399 - 472

Published: Aug. 24, 2023

Cell excitability and its modulation by hormones neurotransmitters involve the concerted action of a large repertoire membrane proteins, especially ion channels. Unique complements coexpressed channels are exquisitely balanced against each other in different excitable cell types, establishing distinct electrical properties that tailored for diverse physiological contributions, dysfunction any component may induce disease state. A crucial parameter controlling is resting potential (RMP) set extra- intracellular concentrations ions, mainly Na + , K Cl − their passive permeation across through leak Indeed, dysregulation RMP causes significant effects on cellular excitability. This review describes molecular channel NALCN, which associates with accessory subunits UNC-79, UNC-80, NLF-1/FAM155 to conduct depolarizing background currents various neurons. Studies animal models clearly demonstrate NALCN contributes fundamental processes nervous system including control respiratory rhythm, circadian sleep, locomotor behavior. Furthermore, associated severe pathological states humans. The critical involvement physiology now well established, but study has been hampered lack specific drugs can block or agonize vitro vivo. Molecular tools available accelerate our understanding how key functions development novel therapies channelopathies.

Language: Английский

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Angiotensin-(1–7) Analogue AVE0991 Modulates Astrocyte-Mediated Neuroinflammation via lncRNA SNHG14/miR-223-3p/NLRP3 Pathway and Offers Neuroprotection in a Transgenic Mouse Model of Alzheimer’s Disease

Journal of Inflammation Research, Journal Year: 2021, Volume and Issue: Volume 14, P. 7007 - 7019

Published: Dec. 1, 2021

Objective: Emerging evidence suggests that brain angiotensin-(1– 7) (Ang-(1– 7)) deficiency contributes to the pathogenesis of Alzheimer's disease (AD). Meanwhile, our previous studies revealed restoration Ang-(1– levels provided neuroprotection by inhibition inflammatory responses during AD progress. However, potential molecular mechanisms which modulates neuroinflammation remain unclear. Materials and Methods: APP/PS1 mice were injected intraperitoneally with AVE0991 (a nonpeptide analogue once a day for 30 consecutive days. Cognitive functions, neuronal synaptic integrity, inflammation-related markers assessed. Since astrocytes played crucial role in AD-related whilst long noncoding RNAs (lncRNAs) reported participate modulating responses, isolated high-throughput lncRNA sequencing identify most differentially expressed following treatment. Afterward, downstream pathways this anti-inflammatory action investigated using primary astrocytes. Results: rescued spatial cognitive impairments alleviated damage mice. The Aβ 1-42 not affected AVE0991. By employing sequencing, vitro study demonstrated first time suppressed astrocytic NLRP3 inflammasome-mediated via SNHG14-dependent manner. SNHG14 acted as sponge miR-223-3p while represented direct target In addition, participated AVE0991-induced suppression inflammasome. Conclusion: Our results suggest inhibits astrocyte-mediated SNHG14/miR-223-3p/NLRP3 pathway offers These findings reveal underlying under condition uncover its Keywords: disease, AVE0991, lncRNAs, SNHG14, miR-223-3p, astrocyte,

Language: Английский

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Computational Methods to Study DNA:DNA:RNA Triplex Formation by lncRNAs

Non-Coding RNA, Journal Year: 2023, Volume and Issue: 9(1), P. 10 - 10

Published: Jan. 21, 2023

Long non-coding RNAs (lncRNAs) impact cell function via numerous mechanisms. In the nucleus, interactions between lncRNAs and DNA consequent formation of non-canonical nucleic acid structures seems to be particularly relevant. Along with single-stranded RNA (ssRNA) (ssDNA), such as R-loops, ssRNA can also interact double-stranded (dsDNA) form DNA:DNA:RNA triplexes. A major challenge in study triplexes is identification precise component interacting specific regions dsDNA. As this a crucial step towards understanding lncRNA function, there exist several computational methods designed predict these sequences. This review summarises recent progress prediction triplex highlights important particular, different tools (Triplexator, LongTarget, TRIPLEXES, Triplex Domain Finder, TriplexFFP, TriplexAligner Fasim-LongTarget) will discussed their use exemplified by selected lncRNAs, whose forming potential was validated experimentally. Collectively, revealed that are likely make contributions gene expression regulation.

Language: Английский

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The endothelial-enriched lncRNA LINC00607 mediates angiogenic function

Basic Research in Cardiology, Journal Year: 2023, Volume and Issue: 118(1)

Published: Jan. 26, 2023

Long non-coding RNAs (lncRNAs) can act as regulatory which, by altering the expression of target genes, impact on cellular phenotype and cardiovascular disease development. Endothelial lncRNAs their vascular functions are largely undefined. Deep RNA-Seq FANTOM5 CAGE analysis revealed lncRNA LINC00607 to be highly enriched in human endothelial cells. was induced response hypoxia, arteriosclerosis regression non-human primates, post-atherosclerotic cultured cells from patients also propranolol used induce arteriovenous malformations. siRNA knockdown or CRISPR/Cas9 knockout attenuated VEGF-A-induced angiogenic sprouting. integrated less into newly formed networks an vivo assay SCID mice. Overexpression CRISPR restored normal function. RNA- ATAC-Seq after changes transcription gene sets linked chromatin accessibility around ERG-binding sites. Mechanistically, interacted with SWI/SNF remodeling protein BRG1. CRISPR/Cas9-mediated BRG1 HUVEC followed CUT&RUN that is required secure a stable state, mainly In conclusion, endothelial-enriched maintains ERG interacting remodeler ultimately mediate angiogenesis.

Language: Английский

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Noncoding RNAs as Key Regulators for Cardiac Development and Cardiovascular Diseases

Journal of Cardiovascular Development and Disease, Journal Year: 2023, Volume and Issue: 10(4), P. 166 - 166

Published: April 12, 2023

Noncoding RNAs (ncRNAs) play fundamental roles in cardiac development and cardiovascular diseases (CVDs), which are a major cause of morbidity mortality. With advances RNA sequencing technology, the focus recent research has transitioned from studies specific candidates to whole transcriptome analyses. Thanks these types studies, new ncRNAs have been identified for their implication CVDs. In this review, we briefly describe classification into microRNAs, long ncRNAs, circular RNAs. We then discuss critical CVDs by citing most up-to-date articles. More specifically, summarize formation heart tube morphogenesis, mesoderm specification, embryonic cardiomyocytes progenitor cells. also highlight that recently emerged as key regulators focusing on six them. believe review concisely addresses perhaps not all but certainly aspects current progress ncRNA Thus, would be beneficial readers obtain picture mechanisms action

Language: Английский

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Long non-coding RNAs as pathophysiological regulators, therapeutic targets and novel extracellular vesicle biomarkers for the diagnosis of inflammatory bowel disease

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116868 - 116868

Published: June 7, 2024

Inflammatory bowel disease (IBD) is a chronic relapsing of the gastrointestinal (GI) system that includes two groups, Crohn's (CD) and ulcerative colitis (UC). To cope with these classes IBD, investigation pathogenic mechanisms discovery new diagnostic therapeutic approaches are crucial. Long non-coding RNAs (lncRNAs) which length longer than 200 nucleotides have indicated significant association pathology IBD strong potential to be used as accurate biomarkers in diagnosing predicting responses treatment. In current review, we aim investigate role lncRNAs development IBD. We first describe recent advances research on dysregulated pathogenesis from perspective epithelial barrier function, intestinal immunity, mitochondrial autophagy. Then, highlight possible translational targets, biomarkers, predictors response colon tissues plasma samples. Finally, discuss extracellular vesicles their lncRNA cargo pathophysiology, diagnosis, treatment

Language: Английский

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MIR503HG: A potential diagnostic and therapeutic target in human diseases

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 160, P. 114314 - 114314

Published: Feb. 2, 2023

LncRNAs are involved in many physiological and pathological processes, including chromatin remodeling, transcription, posttranscriptional gene expression, mRNA stability, translation, posttranslational modification, their functions depend on subcellular localization. MIR503HG is a lncRNA as well host for the miRNAs miR-503 miR-424. independently or synergistically with miR-503. affects cell proliferation, invasion, metastasis, apoptosis, angiogenesis, other biological behaviors. The mechanism of disease includes interaction protein, sponging miRNA to regulate downstream target gene, participation NF-κB, TGF-β, ERK/MAPK, PI3K/AKT signaling pathways. In this review, we summarize molecular mechanisms its potential applications diagnosis, prognosis, treatment. We also raise some unanswered questions area, providing insights future research.

Language: Английский

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Human myofiber‐enriched aging‐induced lncRNAFRAIL1 promotes loss of skeletal muscle function

Aging Cell, Journal Year: 2024, Volume and Issue: 23(4)

Published: Jan. 31, 2024

Abstract The loss of skeletal muscle mass during aging is a significant health concern linked to adverse outcomes in older individuals. Understanding the molecular basis age‐related crucial for developing strategies combat this debilitating condition. Long noncoding RNAs (lncRNAs) are largely uncharacterized class biomolecules that have been implicated cellular homeostasis and dysfunction across many tissues cell types. To identify lncRNAs might contribute aging, we screened whose expression was altered vastus lateralis from compared young adults. We identified FRAIL1 as an aging‐induced lncRNA with high abundance human muscle. In healthy adults, increased age conjunction lower function. Forced mouse tibialis anterior elicits dose‐dependent reduction fiber size independent changes type. Furthermore, dependent on intact region highly conserved non‐human primates. Unbiased transcriptional proteomic profiling effects revealed widespread mRNA protein recapitulate pathways processes known be Taken together, these findings shed light intricate mechanisms underlying implicate phenotypes.

Language: Английский

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Long noncoding RNAs in cardiometabolic disorders

FEBS Letters, Journal Year: 2022, Volume and Issue: 596(11), P. 1367 - 1387

Published: May 9, 2022

The advancement of medical technology has led not only to an increase in life expectancy but also a rise aging-related diseases. Aging promotes metabolic disorders, turn affecting cardiovascular health. Derailment biological processes the pancreas, liver, adipose tissue, and skeletal muscle impairs glucose lipid metabolism, mitochondrial function, triggering development diabetes lipid-related disorders that inflict damage on cardiac vascular tissues. Long noncoding RNAs (lncRNAs) regulate wide range process are one key factors controlling metabolism mitochondria. Here, we discuss versatile function lncRNAs involved regulation lipid, how dysregulation induces various their consequences.

Language: Английский

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