A comprehensive repertoire of tRNA-derived fragments in prostate cancer

Abstract

Prostate cancer (PCa) is the most common cancer among men in developed countries. Although its genetic background is thoroughly investigated, rather little is known about the role of small non-coding RNAs (sncRNA) in this disease. tRNA-derived fragments (tRFs) represent a new class of sncRNAs, which are present in a broad range of species and have been reported to play a role in several cellular processes. Here, we analyzed the expression of tRFs in fresh frozen patient samples derived from normal adjacent prostate and different stages of PCa by RNA-sequencing. We identified 598 unique tRFs, many of which are deregulated in cancer samples when compared to normal adjacent tissue. Most of the identified tRFs are derived from the 5’- and 3’-ends of mature cytosolic tRNAs, but we also found tRFs produced from other parts of tRNAs, including pre-tRNA trailers and leaders, as well as tRFs from mitochondrial tRNAs. The 5’-derived tRFs comprise the most abundant class of tRFs in general and represent the major class among upregulated tRFs. The 3’-derived tRFs types are dominant among downregulated tRFs in PCa. We validated the expression of three tRFs using qPCR. The ratio of tRFs derived from tRNALysCTT and tRNAPheGAA emerged as a good indicator of progression-free survival and a candidate prognostic marker. This study provides a systematic catalogue of tRFs and their dysregulation in PCa and can serve as the basis for further research on the biomarker potential and functional roles of tRFs in this disease.

MicroRNAs and tRNA-derived fragments predict the transformation of myelodysplastic syndromes to acute myeloid leukemia

“…Since each tRNA family may be composed of several isotypes (anticodons) and individual sequences (different tRNA sequences for each anticodon), this appears to be non-random differential cleavage, as has been shown previously. 27,29,31,32 Group C had significantly more tDRs for Val (adjusted p = 0.01) and Gly (adjusted p = 0.017). In addition, there was a proportionately higher fraction of reads aligned to positions 46-72 in Groups A and B than in Group C, with greater representation of phenylalanine-encoding tDRs in Group B (adjusted p = 9.3E-05 for C versus B).…”

“…There are two discrete populations of tDRs, one of 33 nucleotide 5’ tDHs that encompasses the D loop with terminal cleavage before the anticodon. 31 The second group is composed of residues 46-72, encompassing the variable loop and the T loop of the full tRNA, similar to the type V set of tRFs that have been previously identified, 32 and may represent truncated 3’ tRHs. In general, only certain tRNA families (coding for the same amino acid) are represented in each group.…”

“…In addition, intermediate tRF species have also been identified without a terminal 5’ or 3’ end from the mature tRNA, such as the V-type series. 32 …”

Identification of two novel functional tRNA-derived fragments induced in response to respiratory syncytial virus infection

“…Unbiased deep sequencing of human sncRNAs has shown the changes of tRFs in response to various types of diseases, including cancer, neuro-developmental disorders and infections; however, the significance of tRFs in diseases and the associated molecular mechanisms remain largely unknown, mainly due to the lack of methods for the functional studies [9,10,[19][20][21]. Following our report on the function of tRF5-GluCTC in regulating RSV replication [10,[22][23][24], many recent studies suggest the role of tRFs in infectious diseases; however, other important tRFs in infectious diseases have not been identified.…”

tRNA-Derived Fragments as Novel Predictive Biomarkers for Trastuzumab-Resistant Breast Cancer

“…Additionally, tRNA halves can prevent apoptosis of cancer cells by binding to cytochrome C or promote the assembly of stress granules that help cells survive in adverse conditions [30]. Another recent study indicated that two specific tRFs derived from tRNA Lys-CTT and tRNA Phe-GAA were good indicators of progression-free survival (PFS) and candidate prognostic markers [31]. Taken together, these findings strongly suggest a functional role for tRNA-derived fragments in cancer progression.…”