Role of tRNA-derived small RNAs(tsRNAs) in the diagnosis and treatment of malignant tumours

Mao, Mingwen; Chen, Weina; Huang, Xingbiao; Ye, Dong

doi:10.1186/s12964-023-01199-w

Cited by 12 publications

(3 citation statements)

References 61 publications

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“…A unique strategy to confer resistance in such plant crops against viruses was envisioned via cytosolic RNase P (cytoRP) technology (Gobert et al, 2021), wherein plant PRORPs were re‐localized to accumulate in the cytoplasm to target TLSs, thereby disrupting viral replication. The tRNA‐derived small RNAs (tsRNAs), a class of small ncRNAs that occur due to processing activities of RNase P and similar processing enzymes, could serve as diagnostic markers to track disease progression (Mao et al, 2023). The disease‐associated pathogenic variants of the three human mt‐RNase P subunits lead to mitochondrial dysfunction in affected individuals displaying variable pleiotropic clinical phenotypes and is characterized by aberrant tRNA processing, insulin resistance, and oxidative phosphorylation (OXPHOS) defects (Chatfield et al, 2015; Hochberg et al, 2021; Hodgkinson et al, 2014; Jung et al, 2023; Metodiev et al, 2016; Rossetti et al, 2021; Sridhara, 2017).…”

Section: Applications Of Rnase Pmentioning

confidence: 99%

Multiple structural flavors of RNase P in precursor tRNA processing

Sridhara

2024

WIREs RNA

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The precursor transfer RNAs (pre‐tRNAs) require extensive processing to generate mature tRNAs possessing proper fold, structural stability, and functionality required to sustain cellular viability. The road to tRNA maturation follows an ordered process: 5′‐processing, 3′‐processing, modifications at specific sites, if any, and 3′‐CCA addition before aminoacylation and recruitment to the cellular protein synthesis machinery. Ribonuclease P (RNase P) is a universally conserved endonuclease in all domains of life, performing the hydrolysis of pre‐tRNA sequences at the 5′ end by the removal of phosphodiester linkages between nucleotides at position −1 and +1. Except for an archaeal species: Nanoarchaeum equitans where tRNAs are transcribed from leaderless‐position +1, RNase P is indispensable for life and displays fundamental variations in terms of enzyme subunit composition, mechanism of substrate recognition and active site architecture, utilizing in all cases a two metal ion‐mediated conserved catalytic reaction. While the canonical RNA‐based ribonucleoprotein RNase P has been well‐known to occur in bacteria, archaea, and eukaryotes, the occurrence of RNA‐free protein‐only RNase P in eukaryotes and RNA‐free homologs of Aquifex RNase P in prokaryotes has been discovered more recently. This review aims to provide a comprehensive overview of structural diversity displayed by various RNA‐based and RNA‐free RNase P holoenzymes towards harnessing critical RNA–protein and protein–protein interactions in achieving conserved pre‐tRNA processing functionality. Furthermore, alternate roles and functional interchangeability of RNase P are discussed in the context of its employability in several clinical and biotechnological applications.This article is categorized under: RNA Processing > tRNA Processing RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes

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Section: Applications Of Rnase Pmentioning

confidence: 99%

Multiple structural flavors of RNase P in precursor tRNA processing

Sridhara

2024

WIREs RNA

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“…Novel among small non-coding RNAs, tsRNAs, derived from mature or pre-tRNAs, span 14 to 30 nucleotides ( Mao et al, 2023 ). These tsRNAs diverge into tRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) ( Gao et al, 2022 ; Chen and Shen, 2021 ; Chu et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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

Wang,

Huang,

Ying

et al. 2024

Front. Genet.

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

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“…This occurs at the transcriptional level by binding transcription factors [11] and at the post-transcriptional level through RNA interference. Recent data have shown that tRFs are abnormally expressed in multiple malignant tumors and related to tumorigenesis [12]. For instance, tRFs may repress protein translation by binding a complementary mRNA target, resembling miRNAs [13].…”

Section: Introductionmentioning

confidence: 99%

tRNA-Derived Fragments as Biomarkers in Bladder Cancer

Strømme,

Heck,

Brede

et al. 2024

Cancers

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Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying noninvasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small noncoding RNA such as transfer RNA-derived fragments (tRF) and microRNA. Here, we performed small-RNA next-generation sequencing from EVs from urine and serum, as well as from serum supernatant. RNA was extracted from 15 non-cancer patients (NCPs) with benign findings in cystoscopy and 41 patients with non-muscle invasive BC. Urine and serum were collected before transurethral resection of bladder tumors (TUR-b) and at routine post-surgery check-ups. We compared levels of tRFs in pre-surgery samples to samples from NCPs and post-surgery check-ups. To further verify our findings, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between T1 stage BC patients and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing pre-surgery to post-surgery samples and four DEtRFs were found when comparing pre-surgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.

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Role of tRNA-derived small RNAs(tsRNAs) in the diagnosis and treatment of malignant tumours

Cited by 12 publications

References 61 publications

Multiple structural flavors of RNase P in precursor tRNA processing

Multiple structural flavors of RNase P in precursor tRNA processing

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

tRNA-Derived Fragments as Biomarkers in Bladder Cancer

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