Abstract
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.
Highlights
The availability of mature transfer RNAs that can deliver amino acids to the ribosome affects protein translation rates [1,2]
The current dogma states that transfer RNAs (tRNAs) 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
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
Summary
The availability of mature transfer RNAs (tRNAs) that can deliver amino acids to the ribosome affects protein translation rates [1,2]. Abnormal expression of tRNAs was shown to support cancer progression and metastasis [9,10,11]. The disease phenotypes of many tRNA-based pathologies are tissue specific [12,13]. Brain malformations and microcephaly are associated with tRNA editing [14], Charcot–Marie–Tooth (CMT) syndrome is linked to mutations in several tRNA synthetase genes [16], and the progression of Huntington disease is affected by the depletion of charged tRNAGln (CUG) [17]. Different tissues and cellular processes were shown to require specific tRNA pool compositions [11,19,20,21,22,23], in multicellular organisms precise spatiotemporal regulation of tRNA levels is complex and is currently poorly understood
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