tRNA biology in health and disease: from expanding proteome diversity to promising biomarkers in medicine
Transfer RNAs are key components of the translation machinery that bring amino acids to the ribosome for protein synthesis. The human genome contains hundreds of tRNA genes but the dynamics of their expression is to date poorly characterized. Primary tRNA transcripts contain 5’-leader, 3’-trailer and intronic regions that are removed in order to obtain mature tRNA sequences of ~75 nt in length which act in translation. In addition, tRNAs need to be post-transcriptionally modified in order to become fully active. tRNAs can also be further processed into smaller RNA species (tRNA-derived fragments: tRFs) that can perform a variety of biological functions (e.g. RNAi pathway, repression of global protein synthesis, etc.). Differential expression of tRNA genes, alterations on tRNA modification patterns and modulation of tRNA processing into tRFs have all been associated to complex human diseases such as metabolic syndromes, neurological disorders and cancer. Thus, studying global tRNA biology has become the focus of attention in recent years.
This talk will be divided into two sections. In the first part, I will present our work on the post-transcriptional modification inosine that is essential for tRNA decoding of the Genetic Code. We show that this modification allows the translation machinery to synthesize Eukarya-specific proteins of both evolutionary and medical relevance. In the second part of the talk, I will introduce tRNA-Seq as a method to study the tRNAome in terms of tRNA expression, processing and modification patterns. This strategy can aid in understanding tRNA biology in health and disease.