Small RNA modifications: regulatory molecules and potential applications

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: June 22, 2023

Abstract Small RNAs (also referred to as small noncoding RNAs, sncRNA) are defined polymeric ribonucleic acid molecules that less than 200 nucleotides in length and serve a variety of essential functions within cells. RNA species include microRNA (miRNA), PIWI-interacting (piRNA), interfering (siRNA), tRNA-derived (tsRNA), etc. Current evidence suggest can also have diverse modifications their nucleotide composition affect stability well capacity for nuclear export, these relevant drive molecular signaling processes biogenesis, cell proliferation differentiation. In this review, we highlight the characteristics cellular modifications, current techniques reliable detection. We discuss how may be clinical applications diagnosis treatment human health conditions such cancer.

Language: Английский

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Paternal phthalate exposure-elicited offspring metabolic disorders are associated with altered sperm small RNAs in mice

Environment International, Journal Year: 2023, Volume and Issue: 172, P. 107769 - 107769

Published: Jan. 23, 2023

Exposure to ubiquitous plastic-associated endocrine disrupting chemicals (EDCs) is associated with the increased risk of many chronic diseases. For example, phthalate exposure cardiometabolic mortality in humans, societal costs ∼ $39 billion/year or more. We recently demonstrated that several widely used EDCs increase disease appropriate mouse models. In addition affecting adult health, parental has also been shown cause metabolic disorders, including obesity and diabetes, offspring. While most studies have focused on impact maternal EDC offspring's little known about effects paternal exposure. current study, we investigated adverse a but understudied phthalate, dicyclohexyl (DCHP) health F1 F2 offspring mice. Paternal DCHP led exacerbated insulin resistance impaired signaling without diet-induced obesity. previously showed sperm small non-coding RNAs tRNA-derived (tsRNAs) rRNA-derived (rsRNAs) contribute intergenerational transmission paternally acquired disorders. Using novel PANDORA-seq, revealed can lead tsRNA/rsRNA landscape changes were undetected by traditional RNA-seq, which may DCHP-elicited effects. Lastly, found sex-specific transgenerational elicited glucose intolerance female descendants. Our results suggest phthalates their These findings our understanding etiology human diseases originating from chemical-elicited

Language: Английский

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tRNA renovatio: Rebirth through fragmentation

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(22), P. 3953 - 3971

Published: Oct. 5, 2023

tRNA function is based on unique structures that enable mRNA decoding using anticodon trinucleotides. These interact with specific aminoacyl-tRNA synthetases and ribosomes 3D shape sequence signatures. Beyond translation, tRNAs serve as versatile signaling molecules interacting other RNAs proteins. Through evolutionary processes, fragmentation emerges not merely random degradation but an act of recreation, generating shorter called tRNA-derived small (tsRNAs). tsRNAs exploit their linear sequences newly arranged for unexpected biological functions, epitomizing the "renovatio" (from Latin, meaning renewal, renovation, rebirth). Emerging methods to uncover full tRNA/tsRNA modifications, combined techniques study RNA integrate AI-powered predictions, will comprehensive investigations products new interaction potentials in relation functions. We anticipate these directions herald a era understanding complexity advancing pharmaceutical engineering.

Language: Английский

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Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 6, 2024

Abstract Background Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in pathogenesis alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack ideal therapeutic strategies for periodontitis that can regenerate while remodeling microenvironment. Quercetin, as monomeric flavonoid, has multiple pharmacological activities, such pro-regenerative, anti-inflammatory, immunomodulatory effects. Despite its vast spectrum quercetin’s clinical application limited due to poor water solubility low bioavailability. Results In this study, we fabricated quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with function continuously releasing quercetin, which could better promote regeneration regulate immune microenvironment compared pure MBG treatment. particular, effectively decreased injection frequency quercetin yielding favorable results. view above excellent effects achieved sustained release further investigated mechanisms. Our findings indicated under microenvironment, intervention restore osteo-/angiogenic capacity periodontal ligament stem cells (PDLSCs), induce regulation macrophages exert an osteoimmunomodulatory effect. Furthermore, also found via be partially blocked overexpression key microRNA——miR-21a-5p, worked through inhibiting expression PDCD4 activating NF-κB signaling pathway. Conclusion summary, our study shows potential approach reconstructing defects it offers new perspective treating miR-21a-5p thereby creating Graphical

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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Emerging Delivery Systems for Enabling Precision Nucleic Acid Therapeutics

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Nucleic acid therapeutics represent a highly promising treatment approach in modern medicine, treating diseases at the genetic level. However, these face numerous challenges practical applications, particularly regarding their stability, effectiveness, cellular uptake efficiency, and limitations delivering them specifically to target tissues. To overcome obstacles, researchers have developed various innovative delivery systems, including viral vectors, lipid nanoparticles, polymer inorganic protein carriers, exosomes, antibody oligonucleotide conjugates, DNA nanostructure-based systems. These systems enhance therapeutic efficacy of nucleic drugs by improving targeting specificity, half-life vivo. In this review, we systematically discuss different types drugs, analyze major barriers encountered delivery, summarize current research progress emerging We also highlight latest advancements application for diseases, infectious cancer, brain wound healing. This review aims provide comprehensive overview drug systems' status future directions integrating nanotechnology, biomaterials science, gene editing technologies, emphasizing transformative potential precision medicine.

Language: Английский

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Emerging functional principles of tRNA-derived small RNAs and other regulatory small RNAs

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(10), P. 105225 - 105225

Published: Sept. 9, 2023

Recent advancements in small RNA sequencing have unveiled a previously hidden world of regulatory noncoding RNAs (sncRNAs) that extend beyond the well-studied interfering RNAs, microRNAs, and piwi-interacting RNAs. This exploration, starting with tRNA-derived has led to discovery diverse universe sncRNAs derived from various longer structured such as rRNAs, nucleolar nuclear Y vault exciting uncharted functional possibilities. In this perspective, we discuss emerging principles well-known RNAi-like mechanisms, focusing on those operate independent linear sequence complementarity but rather function an aptamer-like fashion. Aptamers use 3D structure for specific interactions ligands are modulated by modifications subcellular environments. Given sncRNA functions widespread present species lacking RNAi, they may represent ancient principle predates RNAi. We propose rethinking origin RNAi its relationship these how complementary mechanisms shape biological processes. Lastly, highlights need caution using mimics research therapeutics, their specificity is not restricted solely sequence.

Language: Английский

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Comprehensive map of ribosomal 2′-O-methylation and C/D box snoRNAs in Drosophila melanogaster

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(6), P. 2848 - 2864

Published: Feb. 28, 2024

Abstract During their maturation, ribosomal RNAs (rRNAs) are decorated by hundreds of chemical modifications that participate in proper folding rRNA secondary structures and therefore function. Along with pseudouridine, methylation the 2′-hydroxyl ribose moiety (Nm) is most abundant modification rRNAs. The majority Nm eukaryotes placed Fibrillarin, a conserved methyltransferase belonging to ribonucleoprotein complex guided C/D box small nucleolar (C/D snoRNAs). These impact interactions between rRNAs, tRNAs mRNAs, some known fine tune translation rates efficiency. In this study, we built first comprehensive map sites Drosophila melanogaster rRNAs using two complementary approaches (RiboMethSeq Nanopore direct RNA sequencing) identified corresponding snoRNAs whole-transcriptome sequencing. We de novo 61 sites, from which 55 supported both sequencing methods, validated expression 106 predicted new or alternative targets for 31 them. Comparison level upon different stresses show only slight but specific variations, indicating relatively stable D. melanogaster. This study paves way investigate snoRNA-mediated 2′-O-methylation on proteostasis whole organism.

Language: Английский

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Mechanical overloading-induced miR-325-3p reduction promoted chondrocyte senescence and exacerbated facet joint degeneration

Arthritis Research & Therapy, Journal Year: 2023, Volume and Issue: 25(1)

Published: April 4, 2023

Abstract Objective Lumbar facet joint (LFJ) degeneration is one of the main causes low back pain (LBP). Mechanical stress leads to exacerbation LFJ degeneration, but underlying mechanism remains unknown. This study was intended investigate induced by mechanical stress. Methods Here, mice primary chondrocytes were used screen for key microRNAs overloading. SA-β-gal staining, qRT-PCR, western blot, and histochemical staining applied detect chondrocyte senescence in vitro vivo. We also a dual-luciferase report assay examine targeting relationship miRNA-325-3p (miR-325-3p) Trp53. By using NSC-207895, p53 activator, we investigated whether miR-325-3p down-regulated trp53 expression reduce senescence. A bipedal standing model performed induce osteoarthritis. Adeno-associated virus (AAV) intraarticularly injected evaluate effect on degeneration. Results observed both human osteoarthritis tissues after bipedally 10 weeks. overloading could promote senescence-associated secretory phenotype (SASP) expression. MicroRNA-array analysis identified that obviously decreased overloading, which further validated fluorescence situ hybridization (FISH) Dual-luciferase showed directly targeted Trp53 its MiR-325-3p rescued vitro, however, NSC-207895 reduced this activating p53/p21 pathway. Intraarticular injection AAV expressing alleviated Conclusion Our findings suggested miR-325-3p, turn activated pathway deteriorated may provide promising therapeutic strategy

Language: Английский

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PANDORA-Seq unveils the hidden small noncoding RNA landscape in atherosclerosis of LDL receptor-deficient mice

Journal of Lipid Research, Journal Year: 2023, Volume and Issue: 64(4), P. 100352 - 100352

Published: March 4, 2023

Small noncoding RNAs (sncRNAs) play diverse roles in numerous biological processes. While the widely used RNA sequencing (RNA-Seq) method has advanced sncRNA discovery, modifications can interfere with complementary DNA library construction process, preventing discovery of highly modified sncRNAs including transfer RNA-derived small (tsRNAs) and ribosomal (rsRNAs) that may have important functions disease development. To address this technical obstacle, we recently developed a novel PANDORA-Seq (Panoramic Display by Overcoming Modification Aborted Sequencing) to overcome modification-elicited sequence interferences. identify associated atherosclerosis development, LDL receptor-deficient (LDLR

Language: Английский

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