- MINTbase: a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments. [PMID: 27153631]
Venetia Pliatsika, Phillipe Loher, Aristeidis G Telonis, Isidore Rigoutsos
Bioinformatics (Oxford, England) 2016:32(16)
4 Citations (Google Scholar as of 2017-04-06)
Abstract: It has been known that mature transfer RNAs (tRNAs) that are encoded in the nuclear genome give rise to short molecules, collectively known as tRNA fragments or tRFs. Recently, we reported that, in healthy individuals and in patients, tRFs are constitutive, arise from mitochondrial as well as from nuclear tRNAs, and have composition and abundances that depend on a person's sex, population origin and race as well as on tissue, disease and disease subtype. Our findings as well as similar work by other groups highlight the importance of tRFs and presage an increase in the community's interest in elucidating the roles of tRFs in health and disease. We created MINTbase, a web-based framework that serves the dual-purpose of being a content repository for tRFs and a tool for the interactive exploration of these newly discovered molecules. A key feature of MINTbase is that it deterministically and exhaustively enumerates all possible genomic locations where a sequence fragment can be found and indicates which fragments are exclusive to tRNA space, and thus can be considered as tRFs: this is a very important consideration given that the genomes of higher organisms are riddled with partial tRNA sequences and with tRNA-lookalikes whose aberrant transcripts can be mistaken for tRFs. MINTbase is extremely flexible and integrates and presents tRF information from multiple yet interconnected vantage points ('vistas'). Vistas permit the user to interactively personalize the information that is returned and the manner in which it is displayed. MINTbase can report comparative information on how a tRF is distributed across all anticodon/amino acid combinations, provides alignments between a tRNA and multiple tRFs with which the user can interact, provides details on published studies that reported a tRF as expressed, etc. Importantly, we designed MINTbase to contain all possible tRFs that could ever be produced by mature tRNAs: this allows us to report on their genomic distributions, anticodon/amino acid properties, alignments, etc. while giving users the ability to at-will investigate candidate tRF molecules before embarking on focused experimental explorations. Lastly, we also introduce a new labeling scheme that is tRF-sequence-based and allows users to associate a tRF with a universally unique label ('tRF-license plate') that is independent of a genome assembly and does not require any brokering mechanism. MINTbase is freely accessible at http://cm.jefferson.edu/MINTbase/. Dataset submissions to MINTbase can be initiated at http://cm.jefferson.edu/MINTsubmit/ email@example.com Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.
- Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies. [PMID: 26325506]
Aristeidis G Telonis, Phillipe Loher, Shozo Honda, Yi Jing, Juan Palazzo, Yohei Kirino, Isidore Rigoutsos
19 Citations (Google Scholar as of 2017-04-06)
Abstract: We analyzed transcriptomic data from 452 healthy men and women representing five different human populations and two races, and, 311 breast cancer samples from The Cancer Genome Atlas. Our studies revealed numerous constitutive, distinct fragments with overlapping sequences and quantized lengths that persist across dozens of individuals and arise from the genomic loci of all nuclear and mitochondrial human transfer RNAs (tRNAs). Surprisingly, we discovered that the tRNA fragments' length, starting and ending points, and relative abundance depend on gender, population, race and also on amino acid identity, anticodon, genomic locus, tissue, disease, and disease subtype. Moreover, the length distribution of mitochondrially-encoded tRNAs differs from that of nuclearly-encoded tRNAs, and the specifics of these distributions depend on tissue. Notably, tRNA fragments from the same anticodon do not have correlated abundances. We also report on a novel category of tRNA fragments that significantly contribute to the differences we observe across tissues, genders, populations, and races: these fragments, referred to as i-tRFs, are abundant in human tissues, wholly internal to the respective mature tRNA, and can straddle the anticodon. HITS-CLIP data analysis revealed that tRNA fragments are loaded on Argonaute in a cell-dependent manner, suggesting cell-dependent functional roles through the RNA interference pathway. We validated experimentally two i-tRF molecules: the first was found in 21 of 22 tested breast tumor and adjacent normal samples and was differentially abundant between health and disease whereas the second was found in all eight tested breast cancer cell lines.