Diversity of human tRNA genes from the 1000-genomes project

Abstract

The sequence diversity of individual human genomes has been extensively analyzed for variations and phenotypic implications for mRNA, miRNA, and long non-coding RNA genes. TRNA (tRNA) also exhibits large sequence diversity in the human genome, but tRNA gene sequence variation and potential functional implications in individual human genomes have not been investigated. Here we capitalize on the sequencing data from the 1000-genomes project to examine the diversity of tRNA genes in the human population. Previous analysis of the reference human genome indicated an unexpected large number of diverse tRNA genes beyond the necessity of translation, suggesting that some tRNA transcripts may perform non-canonical functions. We found 24 new tRNA sequences in>1% and 76 new tRNA sequences in>0.2% of all individuals, indicating that tRNA genes are also subject to evolutionary changes in the human population. Unexpectedly, two abundant new tRNA genes contain base-pair mismatches in the anticodon stem. We experimentally determined that these two new tRNAs have altered structures in vitro; however, one new tRNA is not aminoacylated but extremely stable in HeLa cells, suggesting that this new tRNA can be used for non-canonical function. Our results show that at the scale of human population, tRNA genes are more diverse than conventionally understood, and some new tRNAs may perform non-canonical, extra-translational functions that may be linked to human health and disease.

RNA Polymerase III Advances: Structural and tRNA Functional Views

“…tRNAs have a unique type and range of influence on the expression of genetic information. Because the gene copy numbers for different tRNA isoacceptors are highly variable among and even within species [8–10], they should be considered as dynamic genetic elements that influence phenotype.…”

A dual fluorescent reporter for the investigation of methionine mistranslation in live cells

“…Isodecoder tRNAs have the same anticodon but different body sequences. The mammalian genomes contain an unexpectedly large number of tRNA isodecoder genes Chan and Lowe 2009;Parisien et al 2013). Isodecoder tRNAs can fine-tune the efficiency of stop codon suppression (Geslain and Pan 2010) or significantly affect ribosome stalling (Ishimura et al 2014).…”

Different types of secondary information in the genetic code

“…tRNAomes are highly variable and plausibly contribute to trait penetrance Phylogenic evidence indicate that the fractional tRNA gene content of the tRNAome, including isoacceptor ratios, can vary significantly among related species and even among individual humans (Marck and Grosjean 2002;Maraia 2012, 2013;Parisien et al 2013). The subsets of tRNA isoacceptors that are substrates for anticodon modifications can also vary even when the modification enzymes themselves are conserved (Lamichhane et al 2011(Lamichhane et al , 2013b.…”

“…The complement of human tRNA genes and their sequence diversity vary among individuals (Iben and Maraia 2013;Parisien et al 2013). As noted above for Lys synonymous codon decoding of pre-proinsulin, the ratio of gene numbers for isodecoder pairs may be relevent to trait penetrance (Iben and Maraia 2013).…”

“…An independent variable is the tRNA complement, which can differ significantly in gene copy number not only among related species (Chan and Lowe 2009;Iben and Maraia 2012) but also in different strains of a single yeast species (Iben et al 2011;Iben and Maraia 2012) and among different humans (Iben and Maraia 2013;Parisien et al 2013). tRNAome variability can be a determinant of expression of specific mRNAs, at least in some microorganisms (Bulmer 1987).…”