Coordination of transcription and processing of tRNA

Coordination of transcription and processing of RNA is a basic principle in regulation of gene expression in eukaryotes. In the case of mRNA, coordination is primarily founded on a co‐transcriptional processing mechanism by which a nascent precursor mRNA undergoes maturation via cleavage and modification by the transcription machinery. A similar mechanism controls the biosynthesis of rRNA. However, the coordination of transcription and processing of tRNA, a rather short transcript, remains unknown. Here, we present a model for high molecular weight initiation complexes of human RNA polymerase III that assemble on tRNA genes and process precursor transcripts to mature forms. These multifunctional initiation complexes may support co‐transcriptional processing, such as the removal of the 5’ leader of precursor tRNA by RNase P. Based on this model, maturation of tRNA is predetermined prior to transcription initiation. In a human cell, type II initiation complexes coordinate transcription and processing of precursor tRNA in defined compartments. These massive multifunctional complexes ensure that the fate of tRNA is predetermined before initiation of transcription. ​