Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies

• DOI: 10.18632/oncotarget.4695
• Publication Date: 2015-09-28T16:51:29Z
• Authors: Aristeidis G. Tel...; Phillipe Loher; Shozo Honda; Yi Jing; Juan Palazzo; Yohei Kirino; Isidore Rigoutsos
• Keywords: Male; 0301 basic medicine; Base Sequence; Models, Genetic; RNA, Mitochondrial; Molecular Sequence Data; Genetic Variation; Breast Neoplasms; Cell Line; 3. Good health; 03 medical and health sciences; Gene Expression Regulation; RNA, Transfer; Cell Line, Tumor; Anticodon; MCF-7 Cells; Cluster Analysis; Humans; Nucleic Acid Conformation; RNA; Female; Transcriptome

// Aristeidis G. Telonis 1 , Phillipe Loher Shozo Honda Yi Jing Juan Palazzo 2 Yohei Kirino and Isidore Rigoutsos Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA Department of Pathology Anatomy Cell Biology, Correspondence to: Rigoutsos, email: Keywords : tRNA fragment, human genome, nuclear tRNA, mitochondrial Argonaute Received June 10, 2015 Accepted 20, Published July 06, Abstract We analyzed transcriptomic data from 452 healthy men women representing five different populations two races, and, 311 breast cancer samples The Cancer Genome Atlas. Our studies revealed numerous constitutive, distinct fragments with overlapping sequences quantized lengths that persist across dozens individuals arise the genomic loci all transfer RNAs (tRNAs). Surprisingly, we discovered fragments’ length, starting ending points, relative abundance depend on gender, population, race also amino acid identity, anticodon, locus, tissue, disease, disease subtype. Moreover, length distribution mitochondrially-encoded tRNAs differs nuclearly-encoded tRNAs, specifics these distributions tissue. Notably, same anticodon do not have correlated abundances. report a novel category significantly contribute to differences observe tissues, genders, populations, races: fragments, referred as i-tRFs, are abundant in wholly internal respective mature can straddle anticodon. HITS-CLIP analysis loaded cell-dependent manner, suggesting functional roles through RNA interference pathway. validated experimentally i-tRF molecules: first was found 21 22 tested tumor adjacent normal differentially between health whereas second eight cell lines.