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      Tissue-Specific Differences in Human Transfer RNA Expression

      1 , 2 , 1 , *

      PLoS Genetics

      Public Library of Science

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          Over 450 transfer RNA (tRNA) genes have been annotated in the human genome. Reliable quantitation of tRNA levels in human samples using microarray methods presents a technical challenge. We have developed a microarray method to quantify tRNAs based on a fluorescent dye-labeling technique. The first-generation tRNA microarray consists of 42 probes for nuclear encoded tRNAs and 21 probes for mitochondrial encoded tRNAs. These probes cover tRNAs for all 20 amino acids and 11 isoacceptor families. Using this array, we report that the amounts of tRNA within the total cellular RNA vary widely among eight different human tissues. The brain expresses higher overall levels of nuclear encoded tRNAs than every tissue examined but one and higher levels of mitochondrial encoded tRNAs than every tissue examined. We found tissue-specific differences in the expression of individual tRNA species, and tRNAs decoding amino acids with similar chemical properties exhibited coordinated expression in distinct tissue types. Relative tRNA abundance exhibits a statistically significant correlation to the codon usage of a collection of highly expressed, tissue-specific genes in a subset of tissues or tRNA isoacceptors. Our findings demonstrate the existence of tissue-specific expression of tRNA species that strongly implicates a role for tRNA heterogeneity in regulating translation and possibly additional processes in vertebrate organisms.


          Transfer RNAs (tRNAs) translate the genetic code of genes into the amino acid sequence of proteins. Most amino acids have two or more codons. Every organism has multiple tRNA species reading the codons for the same amino acid (tRNA isoacceptors). In bacteria and yeast, differences in the relative abundance of tRNA isoacceptors have been found to affect the level of highly expressed proteins. This tRNA abundance–codon distribution relationship can have predictive power on the expression of genes based on their codon usages. Approximately 450 tRNA genes consisting of 49 isoacceptors and 274 different sequences have been annotated in the human genome. This work describes the first comparative analysis of tRNA expression levels in eight human tissues using microarray methods. The authors find significant, tissue-specific differences in the expression of tRNA species and coordinated expression among tRNAs decoding amino acids with similar chemical properties in distinct tissue types. Correlation of relative tRNA abundance versus the codon usage of highly expressed, tissue-specific genes can be found among a subset of tissues or tRNA isoacceptors. Differential tRNA expression in human tissues suggests that tRNA may play a unique role in regulating translation and possibly other processes in humans.

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          Most cited references 36

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          Initial sequencing and analysis of the human genome.

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          The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
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            CLUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W. The new system is easy to use, providing an integrated system for performing multiple sequence and profile alignments and analysing the results. CLUSTAL X displays the sequence alignment in a window on the screen. A versatile sequence colouring scheme allows the user to highlight conserved features in the alignment. Pull-down menus provide all the options required for traditional multiple sequence and profile alignment. New features include: the ability to cut-and-paste sequences to change the order of the alignment, selection of a subset of the sequences to be realigned, and selection of a sub-range of the alignment to be realigned and inserted back into the original alignment. Alignment quality analysis can be performed and low-scoring segments or exceptional residues can be highlighted. Quality analysis and realignment of selected residue ranges provide the user with a powerful tool to improve and refine difficult alignments and to trap errors in input sequences. CLUSTAL X has been compiled on SUN Solaris, IRIX5.3 on Silicon Graphics, Digital UNIX on DECstations, Microsoft Windows (32 bit) for PCs, Linux ELF for x86 PCs, and Macintosh PowerMac.
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              tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence.

              We describe a program, tRNAscan-SE, which identifies 99-100% of transfer RNA genes in DNA sequence while giving less than one false positive per 15 gigabases. Two previously described tRNA detection programs are used as fast, first-pass prefilters to identify candidate tRNAs, which are then analyzed by a highly selective tRNA covariance model. This work represents a practical application of RNA covariance models, which are general, probabilistic secondary structure profiles based on stochastic context-free grammars. tRNAscan-SE searches at approximately 30 000 bp/s. Additional extensions to tRNAscan-SE detect unusual tRNA homologues such as selenocysteine tRNAs, tRNA-derived repetitive elements and tRNA pseudogenes.

                Author and article information

                Role: Editor
                PLoS Genet
                PLoS Genetics
                Public Library of Science (San Francisco, USA )
                December 2006
                22 December 2006
                13 November 2006
                : 2
                : 12
                [1 ] Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, United States of America
                [2 ] Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America
                North Carolina State University, United States of America
                Author notes
                * To whom correspondence should be addressed. E-mail: taopan@
                06-PLGE-RA-0311R3 plge-02-12-17
                Copyright: © 2006 Dittmar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 9
                Research Article
                Evolutionary Biology
                Genetics and Genomics
                Genetics and Genomics
                Homo (Human)
                Custom metadata
                Dittmar KA, Goodenbour JM, Pan T (2006) Tissue-specific differences in human transfer RNA expression. PLoS Genet 2(12): e221. doi: 10.1371/journal.pgen.0020221



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