Transfer RNAs-derived small RNAs and their application potential in multiple diseases

Chu, Xiaohua; He, Chenyang; Sang, Bo; Yang, Chaofei; Chen, Yin; Ji, Mili; Qian, Airong

doi:10.3389/fcell.2022.954431

Cited by 17 publications

(8 citation statements)

References 155 publications

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“…Most recently, this list of non-canonical functions has expanded due to the discoveries of tRNA fragments that serve numerous unanticipated roles in biology. The rapid pace of the discoveries and the important roles of the tRNA fragments in gene expression, development, and health have been summarized in numerous excellent review articles (Anderson and Ivanov 2014;Kumar et al 2016;Oberbauer and Schaefer 2018;Guzzi and Bellodi 2020;Kim et al 2020;Xie et al 2020;Chu et al 2022;George et al 2022;Hou et al 2022;Pekarsky et al 2022). We direct the reader to these reviews regarding the roles of tRNA fragments in development, health and disease.…”

Section: Trna Fragments and Regulation Of Gene Expressionmentioning

confidence: 99%

The life and times of a tRNA

Phizicky

Hopper

2023

RNA

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The study of eukaryotic tRNA processing has given rise to an explosion of new information and insights in the last several years. We now have unprecedented knowledge of each step in the tRNA processing pathway, revealing unexpected twists in biochemical pathways, multiple new connections with regulatory pathways, and numerous biological effects of defects in processing steps that have profound consequences throughout eukaryotes, leading to growth phenotypes in the yeast Saccharomyces cerevisiae and to neurological and other disorders in humans. This review highlights seminal new results within the pathways that comprise the life of a tRNA, from its birth after transcription until its death by decay. We focus on new findings and revelations in each step of the pathway including the end-processing and splicing steps, many of the numerous modifications throughout the main body and anticodon loop of tRNA that are so crucial for tRNA function, the intricate tRNA trafficking pathways, and the quality control decay pathways, as well as the biogenesis and biology of tRNA-derived fragments. We also describe the many interactions of these pathways with signaling and other pathways in the cell.

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Section: Trna Fragments and Regulation Of Gene Expressionmentioning

confidence: 99%

The life and times of a tRNA

Phizicky

Hopper

2023

RNA

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“…LeuCAG3 tsRNA can promote hepatocellular carcinogenesis by binding to two ribosomal protein mRNAs (RPS28 and RPS15) to enhance their translation [16]. Likewise, previous studies have also identified multiple tRFs involved in various aspects of prostate cancer [17]. tRNA-halves (also called SHOT-RNAs) from tRNA Asp-GUC , tRNA His-GUG , and tRNA Lys-CUU have been noted as promoters of cellular proliferation in breast cancer and PRAD in a sex hormone-dependent manner [18].…”

Section: Introductionmentioning

confidence: 91%

tRNA-Derived RNA Fragments Are Novel Biomarkers for Diagnosis, Prognosis, and Tumor Subtypes in Prostate Cancer

Liu

Cheng

et al. 2023

Current Oncology

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Background: tRNA-derived RNA fragments (tRFs) are a novel class of small ncRNA that are derived from precursor or mature tRNAs. Recently, the general relevance of their roles and clinical values in tumorigenesis, metastasis, and recurrence have been increasingly highlighted. However, there has been no specific systematic study to elucidate any potential clinical significance for these tRFs in prostate adenocarcinoma (PRAD), one of the most common and malignant cancers that threatens male health worldwide. Here, we investigate the clinical value of 5′-tRFs in PRAD. Methods: Small RNA sequencing data were analyzed to discover new 5′-tRFs biomarkers for PRAD. Machine learning algorithms were used to identify 5′-tRF classifiers to distinguish PRAD tumors from normal tissues. LASSO and Cox regression analyses were used to construct 5′-tRF prognostic predictive models. NMF and consensus clustering analyses were performed on 5′-tRF profiles to identify molecular subtypes of PRAD. Results: The overall levels of 5′-tRFs were significantly upregulated in the PRAD tumor samples compared to their adjacent normal samples. tRF classifiers composed of 13 5′-tRFs achieved AUC values as high as 0.963, showing high sensitivity and specificity in distinguishing PRAD tumors from normal samples. Multiple 5′-tRFs were identified as being associated with the PRAD prognosis. The tRF score, defined by a set of eight 5′-tRFs, was highly predictive of survival in PRAD patients. The combination of tRF and Gleason scores showed a significantly better performance than the Gleason score alone, suggesting that 5′-tRFs can offer PRAD patients additional and improved prognostic information. Four molecular subtypes of the PRAD tumor were identified based on their 5′-tRF expression profiles. Genetically, these 5′-tRFs PRAD tumor subtypes exhibited distinct genomic landscapes in tumor cells. Clinically, they showed marked differences in survival and clinicopathological features. Conclusions: 5′-tRFs are potential clinical biomarkers for the diagnosis, prognosis, and classification of tumor subtypes on a molecular level. These can help clinicians formulate personalized treatment plans for PRAD patients and may have similar potential applications for other disease types.

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“…tRF-5 can be generated by Dicer cleaving the D-loop, D stem, or 5’ half of the anticodon stem of mature tRNAs. According to its different cleavage sites, tRF-5 can be categorized into three specific subtypes: (1) tRF-5a (14–16 nt); (2) tRF-5b (22–24 nt); (3) tRF-5c (28–30 nt) [ 58 ]. tRF-2 and i-tRF are recently discovered atypical tsRNAs derived from tRNAs, produced by nuclear-encoded and mitochondrial-encoded tRNAs, present in different tissues and individuals [ 56 , 59 ].…”

Section: Discovery Biogenesis and Regulatory Mechanism Of Tsrnasmentioning

confidence: 99%

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

Zhou,

He,

Zhang

et al. 2024

Mol Cancer

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

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Transfer RNAs-derived small RNAs and their application potential in multiple diseases

Cited by 17 publications

References 155 publications

The life and times of a tRNA

The life and times of a tRNA

tRNA-Derived RNA Fragments Are Novel Biomarkers for Diagnosis, Prognosis, and Tumor Subtypes in Prostate Cancer

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

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