Transfer RNAs play a key role in protein synthesis. Following transcription, tRNAs are extensively processed prior to their departure from the nucleus to become fully functional during translation. This includes removal of 5′ leaders and 3′ trailers by a specific endo- and/or exonuclease, 3′ CCA tail addition, posttranscriptional modifications and in some cases intron removal. In this minireview, the critical factors of nuclear tRNA trafficking are described based on studies in classical models such as yeast and human cell lines. In addition, recent findings and identification of novel regulatory loops of nuclear tRNA trafficking in trypanosomes are discussed with emphasis on tRNA modifications. The comparison between the representatives of opisthokonts and excavates serves here to understand the evolutionary conservation and diversity of nuclear tRNA export mechanisms.

Faculty of Science University of South Bohemia České Budějovice Czech Republic

Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czech Republic

Zobrazit více v PubMed

Bühlmann M, Walrad P, Rico E, Ivens A, Capewell P, Naguleswaran A, Roditi I and Matthews KR (2015) NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway. Nucleic Acids Research 43, 4491–4504. PubMed PMC

Calado A, Treichel N, Müller E-C, Otto A and Kutay U (2002) Exportin-5-mediated nuclear export of eukaryotic elongation factor 1A and tRNA. The EMBO Journal 21, 6216–6224. PubMed PMC

Chafe SC, Pierce JB, Eswara MBK, McGuire AT and Mangroo D (2011) Nutrient stress does not cause retrograde transport of cytoplasmic tRNA to the nucleus in evolutionarily diverse organisms. Molecular Biology of the Cell 22, 1091–1103. PubMed PMC

Chatterjee K, Majumder S, Wan Y, Shah V, Wu J, Huang H and Hopper AK (2017) Sharing the load : Mex67 – Mtr2 cofunctions with Los1 in primary tRNA nuclear export. pp. 2186–2198. PubMed PMC

Chatterjee K, Nostramo RT, Wan Y and Hopper AK (2018) tRNA dynamics between the nucleus, cytoplasm and mitochondrial surface: location, location, location. Biochimica et Biophysica Acta – Gene Regulatory Mechanisms 1861, 373–386. PubMed PMC

Cristodero M, Brogli R, Joss O, Schimanski B, Schneider A and Polacek N (2021) tRNA 3′ shortening by LCCR4 as a response to stress in Trypanosoma brucei. Nucleic Acids Research 49, 1647–1661. PubMed PMC

Daniels J-P, Gull K and Wickstead B (2010) Cell biology of the trypanosome genome. Microbiology and Molecular Biology Reviews : MMBR 74, 552–569. PubMed PMC

Dhakal R, Tong C, Anderson S, Kashina AS, Cooperman B and Bau HH (2019) Dynamics of intracellular stress-induced tRNA trafficking. Nucleic Acids Research 47, 2002–2010. PubMed PMC

Dostalova A, Käser S, Cristodero M and Schimanski B (2013) The nuclear mRNA export receptor Mex67-Mtr2 of Trypanosoma brucei contains a unique and essential zinc finger motif. Molecular Microbiology 88, 728–739. PubMed

Fenn K and Matthews KR (2007) The cell biology of Trypanosoma brucei differentiation. Current Opinion in Microbiology 10, 539–546. PubMed PMC

Fricker R, Brogli R, Luidalepp H, Wyss L, Fasnacht M, Joss O, Zywicki M, Helm M, Schneider A, Cristodero M and Polacek N (2019) A tRNA half modulates translation as stress response in Trypanosoma brucei. Nature Communications 10, 118. PubMed PMC

Hegedűsová E, Kulkarni S, Burgman B, Alfonzo JD and Paris Z (2019) The general mRNA exporters Mex67 and Mtr2 play distinct roles in nuclear export of tRNAs in Trypanosoma brucei. Nucleic Acids Research 47, 8620–8631. PubMed PMC

Hopper AK and Nostramo RT (2019) TRNA processing and subcellular trafficking proteins multitask in pathways for other RNAs. Frontiers in Genetics 10, 1–14. PubMed PMC

Huang HY and Hopper AK (2015) In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic. Genes and Development 29, 772–783. PubMed PMC

Kessler AC, Kulkarni SS, Paulines MJ, Rubio MAT, Limbach PA, Paris Z and Alfonzo JD (2017) Retrograde nuclear transport from the cytoplasm is required for tRNATyr maturation in T. brucei. RNA Biology 15, 528–536. PubMed PMC

Kramer EB and Hopper AK (2013) Retrograde transfer RNA nuclear import provides a new level of tRNA quality control in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the USA 110, 21042–21047. PubMed PMC

Niemann M, Harsman A, Mani J, Peikert CD, Oeljeklaus S and Warscheid B (2017) tRNAs and proteins use the same import channel for translocation across the mitochondrial outer membrane of trypanosomes. 114, E7679–E7687. PubMed PMC

Nostramo RT and Hopper AK (2020) A novel assay provides insight into tRNAPhe retrograde nuclear import and re-export in S. cerevisiae. Nucleic Acids Research 48, 11577–11588. PubMed PMC

Ohira T and Suzuki T (2011) Retrograde nuclear import of tRNA precursors is required for modified base biogenesis in yeast. Proceedings of the National Academy of Sciences of the USA 108, 10502–7. PubMed PMC

Okamura M, Inose H and Masuda S (2014) RNA export through the NPC in eukaryotes. Genes 6, 124–149. PubMed PMC

Rubio MAT, Paris ZZ, Gaston KW, Fleming IMC, Sample P, Trotta CR and Alfonzo JD (2013) Unusual non-canonical intron editing is important for tRNA splicing in Trypanosoma brucei. Molecular Cell 52, 184–192. PubMed PMC

Schwenzer H, Jühling F, Chu A, Pallett LJ, Baumert TF, Maini M and Fassati A (2019) Oxidative stress triggers selective tRNA retrograde transport in human cells during the integrated stress response. Cell Reports 26, 3416–3428, e5. PubMed PMC

Shaheen HH and Hopper AK (2005) Retrograde movement of tRNAs from the cytoplasm to the nucleus in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the USA 102, 11290–11295, PubMed PMC

Takano A, Endo T and Yoshihisa T (2005) tRNA actively shuttles between the nucleus and cytosol in yeast. Science (New York, N.Y.) 309, 140–142. PubMed

Tan THP, Pach R, Crausaz A, Ivens A and Schneider A (2002) tRNAs in Trypanosoma brucei: genomic organization, expression, and mitochondrial import. Molecular and Cellular Biology 22, 3707–3717. PubMed PMC

Whitney ML, Hurto RL, Shaheen HH and Hopper AK (2007) Rapid and reversible nuclear accumulation of cytoplasmic tRNA in response to nutrient availability. Molecular Biology of the Cell 18, 2678–2686. PubMed PMC

Wu J, Bao A, Chatterjee K, Wan Y and Hopper AK (2015) Genome-wide screen uncovers novel pathways for tRNA processing and nuclear–cytoplasmic dynamics. Genes and Development 29, 2633–2644. PubMed PMC

Yoshihisa T, Yunoki-Esaki K, Ohshima C, Tanaka N and Endo T (2003) Possibility of cytoplasmic pre-tRNA splicing: the yeast tRNA splicing endonuclease mainly localizes on the mitochondria. Molecular Biology of the Cell 14, 3266–3279. PubMed PMC

Yoshihisa T, Ohshima C, Yunoki-Esaki K and Endo T (2007) Cytoplasmic splicing of tRNA in Saccharomyces cerevisiae. Genes to Cells : Devoted to Molecular & Cellular Mechanisms 12, 285–297. PubMed

Kinetoplastid cell biology and genetics, from the 2020 British Society for Parasitology Trypanosomiasis and Leishmaniasis symposium, Granada, Spain