Regulatory roles of tRNA-derived RNA fragments in human pathophysiology

Pandey, Kush Kumar; Madhry, Deeksha; Kumar, Yogesh; Malvankar, Shivani; Sapra, Leena; Srivastava, Rupesh K.; Bhattacharyya, Sankar; Verma, Bhupendra

doi:10.1016/j.omtn.2021.06.023

Cited by 46 publications

(30 citation statements)

References 116 publications

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“…The roles of tiRNAs in relevant pathways such as NF-κB, IFN, and Wnt/β-Catenin also suggest their role in immune responses [95]. For instance, the activation of Toll-like receptor 4 (TLR-4) with bacterial lipopolysaccharides (LPS) induces a signalling cascade that enhances NF-κB activation and promotes the expression of ANG exonuclease.…”

Section: Role Of Tirna On Immunity and Their Potential As Cross-speci...mentioning

confidence: 99%

tiRNAs: Insights into Their Biogenesis, Functions, and Future Applications in Livestock Research

Sarais

Perdomo‐Sabogal

Wimmers

et al. 2022

ncRNA

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Transfer RNA (tRNA)-derived small RNAs (tsRNAs) belong to a group of transfer ribonucleic acid (tRNA)-derived fragments that have recently gained interest as molecules with specific biological functions. Their involvement in the regulation of physiological processes and pathological phenotypes suggests molecular roles similar to those of miRNAs. tsRNA biogenesis under specific physiological conditions will offer new perspectives in understanding diseases, and may provide new sources for biological marker design to determine and monitor the health status of farm animals. In this review, we focus on the latest discoveries about tsRNAs and give special attention to molecules initially thought to be mainly associated with tRNA-derived stress-induced RNAs (tiRNAs). We present an outline of their biological functions, offer a collection of useful databases, and discuss future research perspectives and applications in livestock basic and applied research.

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Section: Role Of Tirna On Immunity and Their Potential As Cross-speci...mentioning

confidence: 99%

tiRNAs: Insights into Their Biogenesis, Functions, and Future Applications in Livestock Research

Sarais

Perdomo‐Sabogal

Wimmers

et al. 2022

ncRNA

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“…tRNA-derived fragments (tRFs) are short non-coding RNAs derived from tRNA, approximately 16–40 nucleotides in length [ 5 ], which originate from mitochondrial or nuclear tRNAs [ 6 ]. Currently, tRFs are known to be involved in various physiological and pathological processes, such as infectious diseases and tumor formation, and in neurodegenerative diseases [ 7 ]. Schimmel reported that the events of tRF production responded to many stresses such as hyperosmotic stress, pro-oncogenic transcription under hypoxia, and regulation of hematopoiesis [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

The tRNA-Derived Fragment tRF-24-V29K9UV3IU Functions as a miRNA-like RNA to Prevent Gastric Cancer Progression by Inhibiting GPR78 Expression

Wang

Huang

Fan

et al. 2022

Journal of Oncology

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Emerging studies have proved that tRNA-derived fragments (tRFs) play vital roles in tumor metastasis; however, the function of tRFs in gastric cancer (GC) remains largely unclear. We investigated the role of tRF-24-V29K9UV3IU in growth and metastasis of GC using a xenograft mouse model. Differential gene expression downstream of tRF-24-V29K9UV3IU was identified by transcriptome sequencing, and interaction was then verified by a dual luciferase reporter and RNA immunoprecipitation. MKN-45 cells were also used to explore the biological functions of tRF-24-V29K9UV3IU in vitro. Here, knockdown of tRF-24-V29K9UV3IU promoted tumor growth and metastasis of GC in vivo. The expression of tRF-24-V29K9UV3IU and E-cadherin (epithelial cell marker) was down-regulated in tumors of mice following tRF-24-V29K9UV3IU knockdown, whereas the mesenchymal cell markers N-cadherin and vimentin displayed an opposite trend. Transcriptome sequencing identified 87 differentially expressed genes (DEGs) down-regulated in the tRF-24-V29K9UV3IU-overexpressed groups compared with the control group. Among them, G-protein–coupled receptor 78 (GPR78), the most significantly down-regulated DEG, was also predicted to be a target of tRF-24-V29K9UV3IU. Moreover, tRF-24-V29K9UV3IU could function as a miRNA-like fragment and bind to AGO2 and directly silence GPR78 expression by complementing with the 3 ′ -untranslated region of the GPR78 mRNA. Functionally, overexpression of tRF-24-V29K9UV3IU significantly suppressed proliferation, migration, and invasion and promoted apoptosis of MKN-45 cells, whereas GPR78 attenuated these effects. Therefore, our data suggest that tRF-24-V29K9UV3IU functions as a miRNA-like fragment to suppress GPR78 expression and thus inhibit GC progression. These observations suggest that the tRF-24-V29K9UV3IU/GPR78 axis serves as a potential therapeutic target in GC.

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“…Hypo-modified tRNAs can also become better substrates for RNase cleavage leading to tRNA fragment generation ( Huang and Hopper, 2016 ; Oberbauer and Schaefer, 2018 ). tRNA fragments are a family of small RNAs that participate in many regulatory processes at the cellular and organismal levels ( Anderson and Ivanov, 2014 ; Schimmel, 2018 ; Pandey et al, 2021 ). In the context of viral infections, tRNAs as well as tRNA fragments may facilitate viral replication ( Jin and Musier-Forsyth, 2019 ; Nunes et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

tRNA abundance, modification and fragmentation in nasopharyngeal swabs as biomarkers for COVID-19 severity

Katanski

Alshammary²,

Huang³

et al. 2022

Front. Cell Dev. Biol.

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Emerging and re-emerging respiratory viruses can spread rapidly and cause pandemics as demonstrated by the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The early human immune responses to respiratory viruses are in the nasal cavity and nasopharyngeal regions. Defining biomarkers of disease trajectory at the time of a positive diagnostic test would be an important tool to facilitate decisions such as initiation of antiviral treatment. We hypothesize that nasopharyngeal tRNA profiles could be used to predict Coronavirus Disease 19 (COVID-19) severity. We carried out multiplex small RNA sequencing (MSR-seq) on residual nasopharyngeal swabs to measure simultaneously full-length tRNA abundance, tRNA modifications, and tRNA fragmentation for the human tRNA response to SARS-CoV-2 infection. We identified distinct tRNA signatures associated with mild symptoms versus severe COVID-19 manifestations requiring hospitalization. These results highlight the utility of host tRNA properties as biomarkers for the clinical outcome of SARS-CoV-2.

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Regulatory roles of tRNA-derived RNA fragments in human pathophysiology

Cited by 46 publications

References 116 publications

tiRNAs: Insights into Their Biogenesis, Functions, and Future Applications in Livestock Research

tiRNAs: Insights into Their Biogenesis, Functions, and Future Applications in Livestock Research

The tRNA-Derived Fragment tRF-24-V29K9UV3IU Functions as a miRNA-like RNA to Prevent Gastric Cancer Progression by Inhibiting GPR78 Expression

tRNA abundance, modification and fragmentation in nasopharyngeal swabs as biomarkers for COVID-19 severity

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