Abstract
Background: tRNA and ARS, tRN-A-RS, pivot the translational machinery. How their aberrances correlate to diseases, neurological conditions, metabolic disorders, and cancer is the purpose of this study. Methods: Information was retrieved from the literature and from databases, such as OMIM and MITOMAP, related to disease and cancer. Changes of expressions of ARSs were assessed from analyzing NGS data available from TCGA, ENCODE and lately from roadmap epigenomics. Results: A total of 647 tRNAs and 37 ARSs reside in the genomic pool of human, aberrant expressions of some of the nuclear tRNAs and cytoplasmic ARSs correlate predominately to cancer, while anomalous pathways in mitochondria relate more to other diseases. tRNA fragments juggle between tumor suppressor and oncogenic pathways. Brain cancer and neurological disorders seem to gain impetus from translation machinery components. However, investigation of the causes of the diseases particularly cancer due to the aberrations continues to be hamstrung by the lack of deep sequencing reads of tRNAs in different cell lines, and this needs to be addressed. Conclusions: Increased cell proliferation requires elevated protein synthesis levels and makes the correlation between tumour cells and deregulated tRN-A-RS components in translation plausible. We draw the network of tRN-A-RS with cancer and other diseases, and present and expand on some of the hypotheses on the underlying molecular mechanisms, opening up new avenues for research.
Highlights
In our recent work on eukaryotic tRNAs, the abundant presence of tRNA structures with dissimilarities to the standard cloverleaf was discussed [1,2]
Modifications are observed in acceptor stem (Acc-Stem), D-stem, D-loop, anticodon stem (Ac-stem), Ac-loop, T-stem and TΨC loop (T-loop)
In tRNAVal these mismatches reach the maximum of 72.77%, followed closely by 67.74% in tRNAGln
Summary
A total of 647 tRNAs and 37 ARSs reside in the genomic pool of human, aberrant expressions of some of the nuclear tRNAs and cytoplasmic ARSs correlate predominately to cancer, while anomalous pathways in mitochondria relate more to other diseases. tRNA fragments juggle between tumor suppressor and oncogenic pathways. A total of 647 tRNAs and 37 ARSs reside in the genomic pool of human, aberrant expressions of some of the nuclear tRNAs and cytoplasmic ARSs correlate predominately to cancer, while anomalous pathways in mitochondria relate more to other diseases. TRNA fragments juggle between tumor suppressor and oncogenic pathways. Brain cancer and neurological disorders seem to gain impetus from translation machinery components. Investigation of the causes of the diseases cancer due to the aberrations continues to be hamstrung by the lack of deep sequencing reads of tRNAs in different cell lines, and this needs to be addressed
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