Characteristics of Transfer RNA-Derived Fragments Expressed during Human Renal Cell Development: The Role of Dicer in tRF Biogenesis

Kazimierczyk, Marek; Wojnicka, Marta; Biala, Ewa; Żydowicz-Machtel, Paulina; Imiolczyk, Barbara; Ostrowski, Tomasz; Kurzyńska-Kokorniak, Anna; Wrzesiński, Jan

doi:10.3390/ijms23073644

Cited by 18 publications

(10 citation statements)

References 50 publications

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“…Similarly in human renal cells, knockdown of Dicer stopped the biogenesis of 3′ tRFs derived from tRNA Arg . The tRF reappeared after transfection of the cells with a plasmid containing the dicer gene further confirming the role of Dicer in its biogenesis (Kazimierczyk et al, 2022). Similarly, Dicer knockdown in human HEK293T cell lines revealed that tRFs and miRNAs were significantly reduced upon Dicer knockdown.…”

Section: Figurementioning

confidence: 56%

tRNA derived small RNAs—Small players with big roles

et al. 2022

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In the past 2 decades, small non-coding RNAs derived from tRNA (tsRNAs or tRNA derived fragments; tRFs) have emerged as new powerful players in the field of small RNA mediated regulation of gene expression, translation, and epigenetic control. tRFs have been identified from evolutionarily divergent organisms from Archaea, the higher plants, to humans. Recent studies have confirmed their roles in cancers and other metabolic disorders in humans and experimental models. They have been implicated in biotic and abiotic stress responses in plants as well. In this review, we summarize the current knowledge on tRFs including types of tRFs, their biogenesis, and mechanisms of action. The review also highlights recent studies involving differential expression profiling of tRFs and elucidation of specific functions of individual tRFs from various species. We also discuss potential considerations while designing experiments involving tRFs identification and characterization and list the available bioinformatics tools for this purpose.

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Section: Figurementioning

confidence: 56%

tRNA derived small RNAs—Small players with big roles

et al. 2022

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“…tRFs are small noncoding RNAs (ncRNAs) that were discovered over the last few years. The implementation of novel improved techniques used for the sequencing of tRFs revealed that miRNA-like tRNA fragments are highly abundant in various cell types [ 33 , 34 ]. For instance, tRF-3003a was identified by sequencing of the OA cartilage in a previous study [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

tRNA-Derived Fragment tRF-5009A Regulates Autophagy and Degeneration of Cartilage in Osteoarthritis via Targeting mTOR

Deng

Long

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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tRNA-derived fragments (tRFs) have been reported to have critical regulatory roles in osteoarthritis (OA). Recent studies have suggested that autophagy promotes the homeostasis of the extracellular matrix of chondrocytes in OA. However, the role of tRFs in posttranscriptional gene regulation during autophagy in OA is unknown. Therefore, we explored the role of tRF-5009A in the posttranscriptional gene regulation of autophagy and cartilage degeneration in OA. Using RNA sequencing, we identified tRF-5009A, the tRNAValCAC-derived fragment, in OA tissues and explored its expression by quantitative reverse transcription PCR and fluorescence in situ hybridization. We further investigated the relationship between the expression of tRF-5009A and clinical factors in OA. Chondrocytes were transfected with a tRF-5009A inhibitor or mimic to determine their functions, including in relation to autophagy and the cartilage phenotype. A rescue experiment and dual-luciferase reporter assay were conducted to determine whether the 3 ′ -untranslated region (UTR) of mTOR contains a tRF-5009A-binding site. tRF-5009A was downregulated in the cartilage of OA knees, especially in damaged areas. mTOR was highly expressed in damaged cartilage and negatively correlated with the expression of tRF-5009A; transfection with a tRF-5009A inhibitor promoted the expression of mTOR and suppressed autophagy, whereas transfection with a tRF-5009A mimic had the opposite effect. A dual-luciferase reporter assay showed that tRF-5009A silenced the expression of mTOR by binding to its 3 ′ -UTR. Thus, tRF-5009A regulates autophagy and cartilage degeneration in OA by targeting mTOR. In summary, these findings provide an additional tool for the clinical diagnosis and novel targeted therapy of OA.

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“…As mentioned, under stress conditions, ANG cleaves tRNAs at the anticodon-loop, producing 5′tiRNAs and 3′tiRNAs [ 22 ], although it was reported that ANG cleaves only a subset of tRNAs. By contrast, the other tiRNAs are ANG-independent [ 29 ], since tiRNAs have been found in ANG knockout cells [ 30 ]. Therefore, other unknown RNases may be involved in the production of tiRNA species.…”

Section: Trna-derived Small Interfering Rnasmentioning

confidence: 99%

Role of the Ribonuclease ONCONASE in miRNA Biogenesis and tRNA Processing: Focus on Cancer and Viral Infections

Menegazzi

Gotte

2022

IJMS

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The majority of transcribed RNAs do not codify for proteins, nevertheless they display crucial regulatory functions by affecting the cellular protein expression profile. MicroRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) are effectors of interfering mechanisms, so that their biogenesis is a tightly regulated process. Onconase (ONC) is an amphibian ribonuclease known for cytotoxicity against tumors and antiviral activity. Additionally, ONC administration in patients resulted in clinical effectiveness and in a well-tolerated feature, at least for lung carcinoma and malignant mesothelioma. Moreover, the ONC therapeutic effects are actually potentiated by cotreatment with many conventional antitumor drugs. This review not only aims to describe the ONC activity occurring either in different tumors or in viral infections but also to analyze the molecular mechanisms underlying ONC pleiotropic and cellular-specific effects. In cancer, data suggest that ONC affects malignant phenotypes by generating tRNA fragments and miRNAs able to downregulate oncogenes expression and upregulate tumor-suppressor proteins. In cells infected by viruses, ONC hampers viral spread by digesting the primer tRNAs necessary for viral DNA replication. In this scenario, new therapeutic tools might be developed by exploiting the action of ONC-elicited RNA derivatives.

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Characteristics of Transfer RNA-Derived Fragments Expressed during Human Renal Cell Development: The Role of Dicer in tRF Biogenesis

Cited by 18 publications

References 50 publications

tRNA derived small RNAs—Small players with big roles

tRNA derived small RNAs—Small players with big roles

tRNA-Derived Fragment tRF-5009A Regulates Autophagy and Degeneration of Cartilage in Osteoarthritis via Targeting mTOR

Role of the Ribonuclease ONCONASE in miRNA Biogenesis and tRNA Processing: Focus on Cancer and Viral Infections

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