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The 'Not-So-Famous Five' in tumorigenesis: tRNAs, tRNA fragments, and tRNA epitranscriptome in concert with AARSs and AIMPs.
- Source :
-
Biochimie . Jul2024, Vol. 222, p45-62. 18p. - Publication Year :
- 2024
-
Abstract
- RNA profiling studies have revealed that ∼75% of the human genome is transcribed to RNA but only a meagre fraction of it is translated to proteins. Majority of transcribed RNA constitute a specialized pool of non-coding RNAs. Human genome contains approximately 506 genes encoding a set of 51 different tRNAs, constituting a unique class of non-coding RNAs that not only have essential housekeeping functions as translator molecules during protein synthesis, but have numerous uncharted regulatory functions. Intriguing findings regarding a variety of non-canonical functions of tRNAs, tRNA derived fragments (tRFs), esoteric epitranscriptomic modifications of tRNAs, along with aminoacyl-tRNA synthetases (AARSs) and ARS-interacting multifunctional proteins (AIMPs), envision a 'peripheral dogma' controlling the flow of genetic information in the backdrop of qualitative information wrung out of the long-live central dogma of molecular biology, to drive cells towards either proliferation or differentiation programs. Our review will substantiate intriguing peculiarities of tRNA gene clusters, atypical tRNA-transcription from internal promoters catalysed by another distinct RNA polymerase enzyme, dynamically diverse tRNA epitranscriptome, intricate mechanism of tRNA-charging by AARSs governing translation fidelity, epigenetic regulation of gene expression by tRNA fragments, and the role of tRNAs and tRNA derived/associated molecules as quantitative determinants of the functional proteome, covertly orchestrating the process of tumorigenesis, through a deregulated tRNA-ome mediating selective codon-biased translation of cancer related gene transcripts. [Display omitted] • Distinct tRNA repertoire undertakes codon-biased translation of cancer linked genes. • tRNA deregulation & mischarging diversify tumor proteome entailing chemo-resistance. • Deregulated 'writers' alter the epitranscriptome & stabilize cancerous tRNA profile. • As part of MSC, AARS-AIMPs play non-canonical oncogenic/tumor-suppressive roles. • tRFs/tRDs fine-tune epigenetic regulation of genes involved in tumour progression. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03009084
- Volume :
- 222
- Database :
- Academic Search Index
- Journal :
- Biochimie
- Publication Type :
- Academic Journal
- Accession number :
- 177751769
- Full Text :
- https://doi.org/10.1016/j.biochi.2024.02.004