Tissue Specific Differences in Human Transfer RNA Expression

Abstract

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, tissuespecific 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.

Maternally transmitted late-onset non-syndromic deafness is associated with the novel heteroplasmic T12201C mutation in the mitochondrial tRNAHis gene

“…The absence of a nuclear modifier TRMU A10S variant in matrilineal relatives and the presence of the heterozygous GJB2 235delC mutation47 in seven matrilineal relatives (five with hearing loss and two with normal hearing) indicated that other nuclear modifier genes may contribute to phenotypic variability and tissue-specific effect. Alternatively, tissue-specific differences in tRNA metabolism may contribute to the development of the deafness phenotype 48 49…”

High levels of tRNA abundance and alteration of tRNA charging by bortezomib in multiple myeloma

“…tRNA microarray experiments were conducted as described previously [3; 10]. A brief description follows.…”

“…A tipped balance in tRNA abundance may be characteristic for cancer. In normal human tissues, however, tRNA abundance can vary by up to 4-fold [3]. It is therefore not yet possible to predict how this balance is perturbed in any particular type of cancer or what effect perturbation will have.…”

“…We hypothesize therefore that tRNA charging levels are altered when myeloma cells are treated with bortezomib. In this study, we used recently developed tRNA-specific microarrays [3; 10] to test these hypotheses on the abundance and charging levels of tRNA in myeloma cells (Fig. 1).…”

“…Fluorescent labeling and array hybridization of tRNA was applied previously to demonstrate the existence of tissue-specific expression of tRNA species in humans, implicating a role for tRNA heterogeneity in regulating translation [3]. To measure relative tRNA charging levels, we used selective oxidation of uncharged tRNA followed by fluorescent labeling of charged tRNA.…”