Preferential import of queuosine-modified tRNAs into Trypanosoma brucei mitochondrion is critical for organellar protein synthesis

0554218 - BC 2022 RIV GB eng J - Článek v odborném periodiku
Kulkarni, Sneha Sunil - Rubio, Mary Anne T. - Hegedüsová, Eva - Ross, R. - Limbach, P.A. - Alfonzo, J. D. - Paris, Zdeněk
Preferential import of queuosine-modified tRNAs into Trypanosoma brucei mitochondrion is critical for organellar protein synthesis.
Nucleic Acids Research. Roč. 49, č. 14 (2021), s. 8247-8260. ISSN 0305-1048. E-ISSN 1362-4962
Grant CEP: GA ČR GJ15-21450Y; GA ČR(CZ) GA20-11585S; GA MŠMT(CZ) EF16_019/0000759
Institucionální podpora: RVO:60077344
Klíčová slova: guanine transglycosylase * energy-metabolism * crystal-structure * messenger-rna * cell biology * translation * nucleosides * expression * queuine * absence
Obor OECD: Parasitology
Impakt faktor: 19.160, rok: 2021
Způsob publikování: Open access
https://academic.oup.com/nar/article/49/14/8247/6318497?login=true

Transfer RNAs (tRNAs) are key players in protein synthesis. To be fully active, tRNAs undergo extensive post-transcriptional modifications, including queuosine (Q), a hypermodified 7-deaza-guanosine present in the anticodon of several tRNAs in bacteria and eukarya. Here, molecular and biochemical approaches revealed that in the protozoan parasite Trypanosoma brucei, Q-containing tRNAs have a preference for the U-ending codons for asparagine, aspartate, tyrosine and histidine, analogous to what has been described in other systems. However, since a lack of tRNA genes in T. brucei mitochondria makes it essential to import a complete set from the cytoplasm, we surprisingly found that Q-modified tRNAs are preferentially imported over their unmodified counter-parts. In turn, their absence from mitochondria has a pronounced effect on organellar translation and affects function. Although Q modification in T. brucei is globally important for codon selection, it is more so for mitochondrial protein synthesis. These results provide a unique example of the combined regulatory effect of codon usage and wobble modifications on protein synthesis, all driven by tRNA intracellular transport dynamics.
Trvalý link: http://hdl.handle.net/11104/0328910