Abstract
BackgroundSmall RNA-sequencing has revealed the diversity and high abundance of small RNAs derived from tRNAs, referred to as tRNA-derived RNAs. However, at present, there is no standardized nomenclature and there are no methods for accurate annotation and quantification of these small RNAs. tRNA-derived RNAs have unique features that limit the utility of conventional alignment tools and quantification methods.ResultsWe describe here the challenges of mapping, naming, and quantifying tRNA-derived RNAs and present a novel method that addresses them, called tDRmapper. We then use tDRmapper to perform a comparative analysis of tRNA-derived RNA profiles across different human cell types and diseases. We found that (1) tRNA-derived RNA profiles can differ dramatically across different cell types and disease states, (2) that positions and types of chemical modifications of tRNA-derived RNAs vary by cell type and disease, and (3) that entirely different tRNA-derived RNA species can be produced from the same parental tRNA depending on the cell type.Conclusion tDRmappernot only provides a standardized nomenclature and quantification scheme, but also includes graphical visualization that facilitates the discovery of novel tRNA and tRNA-derived RNA biology.
Highlights
Small RNA-sequencing has revealed the diversity and high abundance of small RNAs derived from transfer RNA (tRNA), referred to as Transfer RNAs (tRNAs)-derived RNAs
Results and discussion tDRmapper aligns small RNA-seq reads to tRNA sequences, allowing for and quantifying mismatches and deletions. tDRmapper was written with its own string matching alignment scheme and does not use a previously developed aligner, such as Bowtie 2 [14]
While Bowtie 2 does allow for mismatches and deletions, it was not designed with unique features of tRNAs and pre-tRNAs in mind. tDRmapper is designed for mapping reads to tRNAs, which have several unique features that are described below
Summary
Small RNA-sequencing has revealed the diversity and high abundance of small RNAs derived from tRNAs, referred to as tRNA-derived RNAs. TRNA-derived RNAs (tDRs) are small RNAs that are enzymatically processed from either nascent pre-tRNA transcripts or mature tRNAs [1]. Their regulated biogenesis and well-defined 5′ and 3′ ends indicate that they are not products of tRNA degradation [2]. Despite the potential biomedical significance of tDRs, the field is lagging behind other small RNA fields in terms of genomic annotation and strategies for quantification from small RNA-sequencing (small RNA-seq) data. This is due in large part to: (a) the unique computational challenges of mapping tDRs from small RNAseq data and (b) the lack of a standardized nomenclature for tDRs
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