Identification of tRNA-derived ncRNAs in TCGA and NCI-60 panel cell lines and development of the public database tRFexplorer

Abstract

Next-generation sequencing is increasing our understanding and knowledge of non-coding RNAs (ncRNAs), elucidating their roles in molecular mechanisms and processes such as cell growth and development. Within such a class, tRNA-derived ncRNAs have been recently associated with gene expression regulation in cancer progression. In this paper, we characterize, for the first time, tRNA-derived ncRNAs in NCI-60. Furthermore, we assess their expression profile in The Cancer Genome Atlas (TCGA). Our comprehensive analysis allowed us to report 322 distinct tRNA-derived ncRNAs in NCI-60, categorized in tRNA-derived fragments (11 tRF-5s, 55 tRF-3s), tRNA-derived small RNAs (107 tsRNAs) and tRNA 5′ leader RNAs (149 sequences identified). In TCGA, we were able to identify 232 distinct tRNA-derived ncRNAs categorized in 53 tRF-5s, 58 tRF-3s, 63 tsRNAs and 58 5′ leader RNAs. This latter group represents an additional evidence of tRNA-derived ncRNAs originating from the 5′ leader region of precursor tRNA. We developed a public database, tRFexplorer, which provides users with the expression profile of each tRNA-derived ncRNAs in every cell line in NCI-60 as well as for each TCGA tumor type. Moreover, the system allows us to perform differential expression analyses of such fragments in TCGA, as well as correlation analyses of tRNA-derived ncRNAs expression in TCGA and NCI-60 with gene and miRNA expression in TCGA samples, in association with all omics and compound activities data available on CellMiner. Hence, the tool provides an important opportunity to investigate their potential biological roles in absence of any direct experimental evidence. Database URL: https://trfexplorer.cloud/

tRNA-derived RNA fragments in cancer: current status and future perspectives

“…Another study identified hundreds of distinct tRFs in the National Cancer Institute 60 (NCI-60) cell lines and TCGA tumor samples. The expression profile of these tRFs was compiled into a public database, tRFexplorer (https://trfexplorer.cloud/) [37]. Another web server, named tRF2Cancer (http://rna.sysu.edu.cn/ tRFfinder/), can be used for identifying tRFs from small RNA sequencing datasets from various cancer types [10].…”

tRNA-Derived Small RNAs: Novel Epigenetic Regulators

“…Taken together, tsRNAs can be processed or generated by enzymatic cleavage at specific sites; this demonstrates that these RNAs are not simple degradation by-products and suggests that different types of tsRNAs have distinct biogenesis and may have distinct biological roles as well. Importantly, although hundreds of tsRNAs have been identified using current high-throughput sequencing technologies [ 9 , 10 , 81 ], no consistent naming conventions have been established, which can serve as a major obstacle in tsRNA research.…”

“…Consequently, tsRNA characterization and annotation guidelines have been developed [ 8 , 9 ]. So far, 232 annotated tsRNAs have been included in the Cancer Genome Atlas (TCGA) and the NCI-60 cell line screen databases [ 10 ], but this number will certainly increase.…”

Mechanisms of tRNA-derived fragments and tRNA halves in cancer treatment resistance

“…Researchers have also established some databases to manage tRFs, such as trfdb (http://genome.bioch. virginia.edu/trfdb) [5], tRF2Cancer (http://rna.sysu.edu.cn/ tRFfinder/) [58], YM500v3 database (http://ngs.ym.edu.tw/ ym500/) [163], tRFexplorer (https://trfexplorer.cloud/) [164], and MINTbase v2.0 (http://cm.jefferson.edu/MINTbase/) [165]. Mitochondrial and Nuclear TRF mapping (MIN-Tmap; https://github.com/TJU-CMC-Org/MINTmap/) is a software package for rapid and detailed identification of tRFs in short RNA-seq datasets.…”