Non-coding RNAs as therapeutic targets and biomarkers in ischaemic heart disease

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 21(8), P. 556 - 573

Published: March 18, 2024

Language: Английский

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tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 15, 2024

Abstract Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding (ncRNAs) produced by the specific cleavage precursor or mature tRNAs. tsRNAs involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting occurrence development human diseases, including cancers. Recent studies have shown that play an important role tumorigenesis regulating behaviors malignant proliferation, invasion metastasis, angiogenesis, immune response, tumor resistance, metabolism reprogramming. These may be potential targets for treatment. Furthermore, can exist abundantly stably bodily fluids (e.g., blood, serum, urine) form free encapsulated extracellular vesicles, intercellular communication microenvironment (TME). Meanwhile, their abnormal expression is closely related to clinicopathological features patients, staging, lymph node poor prognosis patients; thus, served novel liquid biopsy biomarker. This review summarizes discovery, production, analyzes molecular mechanisms applications therapy, which provide strategies early diagnosis targeted therapy tumors.

Language: Английский

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RNA modifying enzymes shape tRNA biogenesis and function

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(8), P. 107488 - 107488

Published: June 20, 2024

Language: Английский

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The tRNA ^Val half: A strong endogenous Toll-like receptor 7 ligand with a 5′-terminal universal sequence signature

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(19)

Published: April 29, 2024

Toll-like receptors (TLRs) are crucial components of the innate immune system. Endosomal TLR7 recognizes single-stranded RNAs, yet its endogenous ssRNA ligands not fully understood. We previously showed that extracellular (ex-) 5′-half molecules tRNA HisGUG (the 5′-tRNA half) in vesicles (EVs) human macrophages activate when delivered into endosomes recipient macrophages. Here, we explored immunostimulatory ex-5′-tRNA half and identified ValCAC/AAC half, most abundant tRNA-derived RNA macrophage EVs, as another molecule with strong activation capacity. Levels were highly up-regulated EVs upon exposure to lipopolysaccharide plasma patients infected Mycobacterium tuberculosis . The half-mediated effectively eradicated bacteria Mutation analyses terminal GUUU sequence a determinant for activation. confirmed is optimal ratio guanosine uridine activation; microRNAs or other RNAs motif can indeed stimulate TLR7, establishing universal signature These results advance our understanding offer insights diverse TLR7-involved pathologies their therapeutic strategies.

Language: Английский

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Small RNA and Toll-like receptor interactions: origins and disease mechanisms

Trends in Biochemical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Functional roles of conserved lncRNAs and circRNAs in eukaryotes

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 9(4), P. 1271 - 1279

Published: June 26, 2024

Long non-coding RNAs (lncRNAs) and circular (circRNAs) have emerged as critical regulators in essentially all biological processes across eukaryotes. They exert their functions through chromatin remodeling, transcriptional regulation, interacting with RNA-binding proteins (RBPs), serving microRNA sponges, etc. Although are typically more species-specific than coding RNAs, a number of well-characterized lncRNA (such

Language: Английский

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Father’s diet influences son’s metabolic health through sperm RNA

Nature, Journal Year: 2024, Volume and Issue: 630(8017), P. 571 - 573

Published: June 5, 2024

Language: Английский

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Exosomes derived from IFNγ-stimulated mesenchymal stem cells protect photoreceptors in RCS rats by restoring immune homeostasis through tsRNAs

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 13, 2024

Retinitis pigmentosa is a neurodegenerative disease with major pathologies of photoreceptor apoptosis and immune imbalance. Mesenchymal stem cells (MSCs) have been approved for clinical application treating various immune-related or diseases. The objective this research was to investigate the mechanisms underlying safeguarding effects MSC-derived exosomes in retinal degenerative model. Interferon gamma-stimulated (IFNγ-Exos) secreted from MSCs were isolated, purified, injected into vitreous body RCS rats on postnatal day (P) 21. Morphological functional changes retina examined at P28, P35, P42, P49 Royal College Surgeons (RCS) rats. mechanism explored using high-throughput sequencing technology confirmed vitro. Treatment IFNγ-Exo produced better protective photoreceptors improved visual function significantly suppressed activated microglia inhibited inflammatory responses rats, which also lipopolysaccharide-activated cell line BV2. Furthermore, through tRNA-derived small RNA (tsRNA) sequencing, we found that IFNγ-Exos contained higher levels Other-1_17-tRNA-Phe-GAA-1-M3, Other-6_23-tRNA-Lys-TTT-3, TRF-57:75-GLN-CGG-2-m2 than native exosomes, mainly regulated pathways, including mTOR signaling pathway EGFR tyrosine kinase inhibitor resistance. IFNγ stimulation enhanced neuroprotective retina, may be mediated by regulatory tsRNAs acting microglia. In conclusion, promising nanotherapeutic agent treatment retinitis pigmentosa.

Language: Английский

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Recognition of the tRNA structure: Everything everywhere but not all at once

Cell chemical biology, Journal Year: 2023, Volume and Issue: 31(1), P. 36 - 52

Published: Dec. 29, 2023

Language: Английский

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Unveiling the role of tRNA-derived small RNAs in MAPK signaling pathway: implications for cancer and beyond

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: March 26, 2024

tRNA-derived small RNAs (tsRNAs) are novel non-coding originating from mature or precursor tRNAs (pre-tRNA), typically spanning 14 to 30 nt. The Mitogen-activated protein kinases (MAPK) pathway orchestrates cellular responses, influencing proliferation, differentiation, apoptosis, and transformation. tsRNAs influence the expression of MAPK signaling by targeting specific proteins within pathway. Presently, four MAPK-linked have implications in gastric cancer (GC) high-grade serous ovarian (HGSOC). Notably, tRF-Glu-TTC-027 tRF-Val-CAC-016 modulate MAPK-related expression, encompassing p38, Myc, ERK, CyclinD1, CyclinB, c-Myc, hindering GC progression via inhibition. Moreover, tRF-24-V29K9UV3IU tRF-03357 remain unexplored mechanisms. KEGG analysis posits varied modulation for diverse non-cancer maladies. high tRF-36-F900BY4D84KRIME tRF-23-87R8WP9IY relates varicose vein (VV) risk. Elevated tiRNA-Gly-GCC-001, tRF-Gly-GCC-012, tRF-Gly-GCC-013, tRF-Gly-GCC-016 target spinal cord injury (SCI)-related brain-derived neurotrophic factor (BDNF), expression. tRF-Gly-CCC-039 associates with diabetes foot sustained healing, while tRF-5014a inhibits autophagy-linked ATG5 diabetic cardiomyopathy (DCM). Additionally, tsRNA-14783 influences keloid formation regulating M2 macrophage polarization. Upregulation tRF-Arg-ACG-007 downregulation tRF-Ser-GCT-008 associated diabetes. tsRNA-04002 alleviates Intervertebral disk degeneration (IDD) PRKCA. tsRNA-21109 Systemic lupus erythematosus (SLE) inhibiting M1 upregulated tiNA-Gly-GCC-002 downregulated tRF-Ala-AGC-010, tRF-Gln-CTG-005 tRF-Leu-AAG-001 may be involved pathogenesis Lupus nephritis (LN) affecting Downregulation tsRNA-1018, tsRNA-3045b, tsRNA-5021a tsRNA-1020 affected pathway, thereby improving Acute lung (ALI). This review comprehensively dissects tsRNA roles across cancers other diseases, illuminating a avenue translational medical exploration.

Language: Английский

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