GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324706/primaryOK200GenomicsMus musculusNon-coding RNA profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324706GEOGSEfalseMitochondrial tRNA-derived fragments link mtDNA variation to metastatic burden [lung]How mitochondrial DNA (mtDNA) polymorphisms influence complex phenotypes remains poorly understood. Using Mitochondrial-Nuclear eXchange (MNX) mice, we previously showed that mtDNA single nucleotide polymorphisms (SNP) modify metastasis, cardiovascular disease, and epigenetic marks independently of metabolic differences, suggesting a role for non-protein-coding loci. The only SNP correlating with these phenotypes resides in the gene encoding mitochondrial tRNA-Arginine (mt-tRNAArg (UCG), mt-TR). Here we identify and preliminarily characterize previously undescribed tRNA-derived fragments (tRF) generated from mt-TR. Northern blotting revealed distinct tRF that are differentially expressed between lung and liver and between sexes. Small RNA sequencing failed to capture these tRF unless samples were pre-treated to enzymatically remove non-canonical RNA termini and base methylation. Focusing on fragments with complete homology to mt-TR, the two most abundant tRF align uniquely to the mitochondrial genome and share conserved cleavage sites. Together, these findings uncover mitochondrial-derived tRF as a previously unrecognized small RNA metastasis modifiers and expand the functional output of the mitochondrial genome, supporting a model in which mtDNA-encoded tRF contribute to phenotype modification.2026/08/07GSE324706GSM9583239GSM9583243GSM9583287GSM9583286GSM9583242GSM9583245GSM9583244GSM9583288GSM9583247GSM9583246GSM9583249GSM9583248GSM9583281GSM9583280GSM9583283GSM9583282GSM9583241GSM9583285GSM9583240GSM9583284GSM9583229GSM9583228GSM9583232GSM9583276GSM9583231GSM9583275GSM9583234GSM9583278GSM9583277GSM9583233GSM9583236GSM9583235GSM9583279GSM9583238GSM9583237GSM9583270GSM9583272GSM9583271GSM9583274GSM9583230GSM9583273GSM9583218GSM9583217GSM9583219GSM9583221GSM9583265GSM9583220GSM9583264GSM9583223GSM9583267GSM9583266GSM9583222GSM9583269GSM9583225GSM9583224GSM9583268GSM9583227GSM9583226GSM9583261GSM9583260GSM9583263GSM9583262GSM9583254GSM9583253GSM9583256GSM9583255GSM9583258GSM9583257GSM9583216GSM9583215GSM9583259GSM9583250GSM9583252GSM958325121626324706Mus musculus