Autophagic degradation of tRNA and extracellular export of modified nucleosides – from phenomenology to molecular understanding
Autophagy is a fundamental process highly conserved from yeast to humans that degrades intracellular components such as proteins and organelles. In this pathway, double membrane-bound structures called autophagosomes encapsulate cargoes and fuse with lysosomes (vacuoles in yeast) highly enriched with hydrolytic enzymes. Recent studies have revealed that in addition to proteins and organelles, RNAs are also degraded by autophagy. Furthermore, a fraction of nucleosides and nucleobases generated as degradation products of RNA is exported into the extracellular space. However, the mechanisms of RNA degradation and extracellular nucleoside/nucleobase export remain unclear. It is evident that rRNA and mRNA are degraded by autophagy, whereas autophagic tRNA degradation has not been reported. It seems also important to export modified nucleosides, which are generated from RNA degradation, into the extracellular space, since they are non-recyclable for nucleic acid and nucleotide synthesis. However, the underlying mechanisms remain to be unveiled. We thus sought to focus on tRNA-derived modified nucleosides exported into the extracellular space and quantitatively analyze them by mass spectrometry, towards a molecular understanding of autophagic tRNA degradation and subsequent extracellular modified nucleoside export. In this colloquium, we would like to present our recent data and discuss about several possibilities on the molecular mechanisms.