tRNA dynamics between the nucleus, cytoplasm and mitochondrial surface: Location, location, location

Abstract

Although tRNAs participate in the essential function of protein translation in the cytoplasm, tRNA transcription and numerous processing steps occur in the nucleus. This subcellular separation between tRNA biogenesis and function requires that tRNAs be efficiently delivered to the cytoplasm in a step termed "primary tRNA nuclear export". Surprisingly, tRNA nuclear-cytoplasmic traffic is not unidirectional, but, rather, movement is bidirectional. Cytoplasmic tRNAs are imported back to the nucleus by the "tRNA retrograde nuclear import" step which is conserved from budding yeast to vertebrate cells and has been hijacked by viruses, such as HIV, for nuclear import of the viral reverse transcription complex in human cells. Under appropriate environmental conditions cytoplasmic tRNAs that have been imported into the nucleus return to the cytoplasm via the 3rd nuclear-cytoplasmic shuttling step termed "tRNA nuclear re-export", that again is conserved from budding yeast to vertebrate cells. We describe the 3 steps of tRNA nuclear-cytoplasmic movements and their regulation. There are multiple tRNA nuclear export and import pathways. The different tRNA nuclear exporters appear to possess substrate specificity leading to the tantalizing possibility that the cellular proteome may be regulated at the level of tRNA nuclear export. Moreover, in some organisms, such as budding yeast, the pre-tRNA splicing heterotetrameric endonuclease (SEN), which removes introns from pre-tRNAs, resides on the cytoplasmic surface of the mitochondria. Therefore, we also describe the localization of the SEN complex to mitochondria and splicing of pre-tRNA on mitochondria, which occurs prior to the participation of tRNAs in protein translation. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.

Reconstitution of the Human tRNA Splicing Endonuclease Complex: insight into the regulation of pre-tRNA cleavage

“…Transfer RNAs (tRNAs) play a critical role in the translation of mRNA into proteins. Eukaryotic tRNA genes are transcribed by RNA Pol III and undergo a series of post-transcriptional processing and modification steps prior to reaching their mature and functional state (1)(2)(3)(4)(5)(6). A subset of tRNA genes contain introns that must be removed during tRNA maturation.…”

Identification of factors that promote biogenesis of tRNACGASer

“…Accordingly, two of the remaining complementation groups consisted of strains carrying mutations in the SES1 or LOS1 gene (Table 1). The essential SES1 gene codes for the seryl-tRNA synthetase that aminoacylates serine tRNA isoacceptors [26] whereas LOS1 encodes a nonessential factor that mediates nuclear export of pre-tRNAs [3,27–29]. One of the two isolated sup61-T47:2C ses1 double mutants (ses1-40) was able to lose the rescuing sup61 + vector at 25°C, generating a strain that is slow-growing at 25°C and inviable at 30°C (Figure 2(a)).…”

“…Eukaryotic transfer RNA genes are transcribed by RNA polymerase III generating precursor tRNAs (pre-tRNAs) that undergo a series of processing steps to generate mature functional tRNAs [1–3]. These steps include the removal of 5´ leader and 3´ trailer sequences, posttranscriptional addition of CCA to the 3´ termini, and the removal of intervening sequences in pre-tRNAs transcribed from intron-containing genes.…”

“…These steps include the removal of 5´ leader and 3´ trailer sequences, posttranscriptional addition of CCA to the 3´ termini, and the removal of intervening sequences in pre-tRNAs transcribed from intron-containing genes. All pre-tRNAs also undergo post-transcriptional modification of a subset of their nucleosides [1–3]. Some modified nucleosides are found in essentially all tRNA species while others are present in a specific or a subclass of tRNAs.…”

“…Some modified nucleosides are found in essentially all tRNA species while others are present in a specific or a subclass of tRNAs. Many pre-tRNA processing steps occur in the nucleus, including end-maturation and numerous nucleoside modifications [1–3]. However, some nucleoside modifications only occur after nuclear export.…”