Cellular dynamics of tRNAs and their genes

Abstract

This discussion focuses on the cellular dynamics of tRNA transcription, processing, and turnover. Early tRNA biosynthesis steps are shared among most tRNAs, while later ones are often individualized for specific tRNAs. In yeast, tRNA transcription and early processing occur coordinately in the nucleolus, requiring topological arrangement of approximately 300 tRNA genes and early processing enzymes to this site; later processing events occur in the nucleoplasm or cytoplasm. tRNA nuclear export requires multiple exporters which function in parallel and the export process is coupled with other cellular events. Nuclear-cytoplasmic tRNA subcellular movement is not unidirectional as a retrograde pathway delivers mature cytoplasmic tRNAs to the nucleus. Despite the long half-lives, there are multiple pathways to turnover damaged tRNAs or normal tRNAs upon cellular stress.

Figure 1

Movement of tRNA between the nucleus and cytoplasm in the yeast, S. cerevisiae. tRNA transcription and initial end processing occurs in the nucleolus. Following various modification steps in the nucleoplasm and at the inner nuclear membrane, intron-containing pre-tRNAs are exported to the cytoplasm via the Los1 exportin and at least one unknown pathway. After pre-tRNA splicing on the cytoplasmic surface of mitochondria, mature tRNAs can be constitutively imported into nuclei, directly or indirectly via Mtr10. Re-export to the cytoplasm is mediated by Los1 and Msn5 and is regulated by nutrient status; likely Msn5-dependent re-export requires that the tRNA be appropriately structured and aminoacylated in the nucleus. Symbols: cloverleaf cartoon – tRNA, green and red balls; parts of the tRNA that are maintained in the mature structure; red balls – anticodon triplet; salmon color balls – transcribed 5’ and 3’ extra sequences; blue balls – intron sequence; aa – amino acid. Processing steps are labeled as are the β-importin members that function in the nucleus-cytoplasm import and export steps.