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@article{2382900,
author = {Kachale, Ambar and Pavlikova, Zuzana and Nenarokova, Anna and Roithova, Adriana and Durante, Ignacio M and Miletinova, Petra and Zahonova, Kristina and Nenarokov, Serafim and Votypka, Jan and Horakova, Eva and Ross, Robert L and Yurchenko, Vyacheslav and Beznoskova, Petra and Paris, Zdenek and Valasek, Leos Shivaya and Lukes, Julius},
article_location = {BERLIN},
article_number = {7945},
doi = {http://dx.doi.org/10.1038/s41586-022-05584-2},
keywords = {Cognate tRNAs; stop codons; Trypanosoma brucei; Saccharomyces cerevisiae; Condylostoma magnum},
language = {eng},
issn = {0028-0836},
journal = {Nature},
title = {Short tRNA anticodon stem and mutant eRF1 allow stop codon reassignment},
url = {https://www.nature.com/articles/s41586-022-05584-2},
volume = {613},
year = {2023}
}
TY - JOUR
ID - 2382900
AU - Kachale, Ambar - Pavlikova, Zuzana - Nenarokova, Anna - Roithova, Adriana - Durante, Ignacio M - Miletinova, Petra - Zahonova, Kristina - Nenarokov, Serafim - Votypka, Jan - Horakova, Eva - Ross, Robert L - Yurchenko, Vyacheslav - Beznoskova, Petra - Paris, Zdenek - Valasek, Leos Shivaya - Lukes, Julius
PY - 2023
TI - Short tRNA anticodon stem and mutant eRF1 allow stop codon reassignment
JF - Nature
VL - 613
IS - 7945
SP - 751-773
EP - 751-773
PB - NATURE PORTFOLIO
SN - 00280836
KW - Cognate tRNAs
KW - stop codons
KW - Trypanosoma brucei
KW - Saccharomyces cerevisiae
KW - Condylostoma magnum
UR - https://www.nature.com/articles/s41586-022-05584-2
N2 - Cognate tRNAs deliver specific amino acids to translating ribosomes according to the standard genetic code, and three codons with no cognate tRNAs serve as stop codons. Some protists have reassigned all stop codons as sense codons, neglecting this fundamental principle(1-4). Here we analyse the in-frame stop codons in 7,259 predicted protein-coding genes of a previously undescribed trypanosomatid, Blastocrithidia nonstop. We reveal that in this species in-frame stop codons are underrepresented in genes expressed at high levels and that UAA serves as the only termination codon. Whereas new tRNAs(Glu) fully cognate to UAG and UAA evolved to reassign these stop codons, the UGA reassignment followed a different path through shortening the anticodon stem of tRNA(CCA)(Trp) from five to four base pairs (bp). The canonical 5-bp tRNA(Trp) recognizes UGG as dictated by the genetic code, whereas its shortened 4-bp variant incorporates tryptophan also into in-frame UGA. Mimicking this evolutionary twist by engineering both variants from B. nonstop, Trypanosoma brucei and Saccharomyces cerevisiae and expressing them in the last two species, we recorded a significantly higher readthrough for all 4-bp variants. Furthermore, a gene encoding B. nonstop release factor 1 acquired a mutation that specifically restricts UGA recognition, robustly potentiating the UGA reassignment. Virtually the same strategy has been adopted by the ciliate Condylostoma magnum. Hence, we describe a previously unknown, universal mechanism that has been exploited in unrelated eukaryotes with reassigned stop codons.
ER -
KACHALE, Ambar, Zuzana PAVLIKOVA, Anna NENAROKOVA, Adriana ROITHOVA, Ignacio M DURANTE, Petra MILETINOVA, Kristina ZAHONOVA, Serafim NENAROKOV, Jan VOTYPKA, Eva HORAKOVA, Robert L ROSS, Vyacheslav YURCHENKO, Petra BEZNOSKOVA, Zdenek PARIS, Leos Shivaya VALASEK and Julius LUKES. Short tRNA anticodon stem and mutant eRF1 allow stop codon reassignment. \textit{Nature}. BERLIN: NATURE PORTFOLIO, 2023, vol.~613, No~7945, p.~751-773. ISSN~0028-0836. Available from: https://dx.doi.org/10.1038/s41586-022-05584-2.
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