Tissue- and Time-Specific Expression of Otherwise Identical tRNA Genes
| Autor: | Gadi Maayan, Roni Rak, Oded Rechavi, Idan Adir, Orna Dahan, Hila Gingold, Dror Sagi, Limor Broday, Yitzhak Pilpel |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Nematoda Gene Expression Biochemistry Aromatic Amino Acids RNA Transfer Invertebrate Genomics Gene expression Amino Acids Promoter Regions Genetic Genetics (clinical) Regulation of gene expression Genetics Genome Organic Compounds Tryptophan Animal Models Genomics Nucleic acids Caenorhabditis Chemistry Organ Specificity Codon usage bias Physical Sciences Transfer RNA Research Article lcsh:QH426-470 Longevity Biology Research and Analysis Methods Genome Complexity 03 medical and health sciences Model Organisms Animals Gene Regulation Caenorhabditis elegans Caenorhabditis elegans Proteins Codon Non-coding RNA Molecular Biology Gene Ecology Evolution Behavior and Systematics Biology and life sciences Organic Chemistry Organisms Chemical Compounds Intron Proteins Computational Biology RNA biology.organism_classification Invertebrates Introns Young Adults lcsh:Genetics 030104 developmental biology Gene Expression Regulation Animal Genomics Age Groups Protein Biosynthesis People and Places Population Groupings |
| Zdroj: | PLoS Genetics, Vol 12, Iss 8, p e1006264 (2016) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Codon usage bias affects protein translation because tRNAs that recognize synonymous codons differ in their abundance. Although the current dogma states that tRNA expression is exclusively regulated by intrinsic control elements (A- and B-box sequences), we revealed, using a reporter that monitors the levels of individual tRNA genes in Caenorhabditis elegans, that eight tryptophan tRNA genes, 100% identical in sequence, are expressed in different tissues and change their expression dynamically. Furthermore, the expression levels of the sup-7 tRNA gene at day 6 were found to predict the animal’s lifespan. We discovered that the expression of tRNAs that reside within introns of protein-coding genes is affected by the host gene’s promoter. Pairing between specific Pol II genes and the tRNAs that are contained in their introns is most likely adaptive, since a genome-wide analysis revealed that the presence of specific intronic tRNAs within specific orthologous genes is conserved across Caenorhabditis species. Author Summary Regulating the expression levels of each tRNA gene is critical: even “silent” mutations, which do not change protein sequences, but change the identity of the tRNA molecules that deliver the amino acid to the ribosome, can lead to protein misfolding and disease. Dynamic changes in the expression of distinct tRNA gene copies are difficult to measure, because tRNAs are transcribed by Pol III, which cannot transcribe fluorescent reporters such as GFP. We used a reporter system that allows monitoring the activity of individual tRNA gene copies in live Caenorhabditis elegans nematodes. Although it is widely believed that tRNA expression is exclusively regulated by intrinsic control elements (A- and B-box sequences), our data revealed that eight tRNA genes, 100% identical in sequence, are distinctively expressed in different tissues, and that they change their expression dynamically. We also found that the expression of tRNAs that reside inside the introns of protein-coding genes is affected by the promoters of the hosting protein-coding genes. In addition, we found a decline in the tRNA expression levels with age, an observation which could be relevant for protein aggregation diseases. Age-related decline in tRNA levels may abrogate co-translational folding, and thus lead to protein misfolding, a hallmark of neurodegeneration. |
| Databáze: | OpenAIRE |
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