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tRF2Cancer: A Web Server to Detect tRNA-derived Small RNA Fragments (tRFs) and Their Expression in Multiple Cancers

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tRF2Cancer: A Web Server to Detect tRNA-derived Small RNA Fragments (tRFs) and Their Expression in Multiple Cancers

Ling-Ling Zheng et al. Nucleic Acids Res.

Abstract

tRNA-derived small RNA fragments (tRFs) are one class of small non-coding RNAs derived from transfer RNAs (tRNAs). tRFs play important roles in cellular processes and are involved in multiple cancers. High-throughput small RNA (sRNA) sequencing experiments can detect all the cellular expressed sRNAs, including tRFs. However, distinguishing genuine tRFs from RNA fragments generated by random degradation remains a major challenge. In this study, we developed an integrated web-based computing system, tRF2Cancer, to accurately identify tRFs from sRNA deep-sequencing data and evaluate their expression in multiple cancers. The binomial test was introduced to evaluate whether reads from a small RNA-seq data set represent tRFs or degraded fragments. A classification method was then used to annotate the types of tRFs based on their sites of origin in pre-tRNA or mature tRNA. We applied the pipeline to analyze 10 991 data sets from 32 types of cancers and identified thousands of expressed tRFs. A tool called 'tRFinCancer' was developed to facilitate the users to inspect the expression of tRFs across different types of cancers. Another tool called 'tRFBrowser' shows both the sites of origin and the distribution of chemical modification sites in tRFs on their source tRNA. The tRF2Cancer web server is available at http://rna.sysu.edu.cn/tRFfinder/.

Figures

Figure 1.
Figure 1.
tRF2Cancer workflow.
Figure 2.
Figure 2.
Analysis of small RNA sequencing reads for identification of tRNA-derived small RNA fragments (tRFs). (A) After cleavage of transfer RNAs (tRNA) at specific positions, small RNA fragments with consistent characteristics are generated. Each of the small RNA could be detected (with certain probability) by sequencing. After mapping sequencing reads back to the tRNA transcripts, most of the reads are distribute within similar regions with significantly higher frequencies at the tRF-5, tRF-3 and tRF-1 regions. (B) Random degradation of tRNA transcripts produces small RNA fragments. When mapped to the tRNA transcripts, it is expected that these random fragments are uniformly distributed across the entire length of source tRNA, and that features of these fragments (such as sites of origin and frequencies of distribution) are inconsistent with those of bona fide tRFs.
Figure 3.
Figure 3.
Demonstration of the biogenesis of different types of tRFs. tRF-1 is generated from the 3′-trailer of primary tRNA. tRF-5, -novel and -3 are produced from the 5′-end, internal and 3′-end of mature tRNA, respectively.
Figure 4.
Figure 4.
Overview of the tRF2Cancer result. (A) The summary table of predicted tRFs results. (B) Detailed information regarding tRFs. (C) The display of sequencing reads distribution on source tRNA. (D) The region of tRFs on tRNA secondary structure. (E) The expression of tRFs in 32 types of cancers. (F) The genome browser for tRF profiling and modification site distribution on source tRNA.

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