Cysteine tRNA acts as a stop codon readthrough-inducing tRNA in the human HEK293T cell line

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F23%3A00576287" target="_blank" >RIV/61388971:_____/23:00576287 - isvavai.cz</a>

Výsledek na webu

<a href="https://rnajournal.cshlp.org/content/29/9/1379" target="_blank" >https://rnajournal.cshlp.org/content/29/9/1379</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1261/rna.079688.123" target="_blank" >10.1261/rna.079688.123</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cysteine tRNA acts as a stop codon readthrough-inducing tRNA in the human HEK293T cell line

Popis výsledku v původním jazyce

Under certain circumstances, any of the three termination codons can be read through by a near-cognate tRNA, i.e., a tRNA whose two out of three anticodon nucleotides base pair with those of the stop codon. Unless programed to synthetize C-terminally extended protein variants with expanded physiological roles, readthrough represents an undesirable translational error. On the other side of a coin, a significant number of human genetic diseases is associated with the introduction of nonsense mutations (premature termination codons [PTCs]) into coding sequences, where stopping is not desirable. Here, the tRNA's ability to induce readthrough opens up the intriguing possibility of mitigating the deleterious effects of PTCs on human health. In yeast, the UGA and UAR stop codons were described to be read through by four readthrough-inducing rti-tRNAs-tRNA(Trp) and tRNA(Cys), and tRNA(Tyr) and tRNA(Gln), respectively. The readthrough-inducing potential of tRNA(Trp) and tRNA(Tyr) was also observed in human cell lines. Here, we investigated the readthrough-inducing potential of human tRNA(Cys) in the HEK293T cell line. The tRNA(Cys) family consists of two isoacceptors, one with ACA and the other with GCA anticodons. We selected nine representative tRNA(Cys) isodecoders (differing in primary sequence and expression level) and tested them using dual luciferase reporter assays. We found that at least two tRNA(Cys) can significantly elevate UGA readthrough when overexpressed. This indicates a mechanistically conserved nature of rti-tRNAs between yeast and human, supporting the idea that they could be used in the PTC-associated RNA therapies.

Název v anglickém jazyce

Cysteine tRNA acts as a stop codon readthrough-inducing tRNA in the human HEK293T cell line

Popis výsledku anglicky

Under certain circumstances, any of the three termination codons can be read through by a near-cognate tRNA, i.e., a tRNA whose two out of three anticodon nucleotides base pair with those of the stop codon. Unless programed to synthetize C-terminally extended protein variants with expanded physiological roles, readthrough represents an undesirable translational error. On the other side of a coin, a significant number of human genetic diseases is associated with the introduction of nonsense mutations (premature termination codons [PTCs]) into coding sequences, where stopping is not desirable. Here, the tRNA's ability to induce readthrough opens up the intriguing possibility of mitigating the deleterious effects of PTCs on human health. In yeast, the UGA and UAR stop codons were described to be read through by four readthrough-inducing rti-tRNAs-tRNA(Trp) and tRNA(Cys), and tRNA(Tyr) and tRNA(Gln), respectively. The readthrough-inducing potential of tRNA(Trp) and tRNA(Tyr) was also observed in human cell lines. Here, we investigated the readthrough-inducing potential of human tRNA(Cys) in the HEK293T cell line. The tRNA(Cys) family consists of two isoacceptors, one with ACA and the other with GCA anticodons. We selected nine representative tRNA(Cys) isodecoders (differing in primary sequence and expression level) and tested them using dual luciferase reporter assays. We found that at least two tRNA(Cys) can significantly elevate UGA readthrough when overexpressed. This indicates a mechanistically conserved nature of rti-tRNAs between yeast and human, supporting the idea that they could be used in the PTC-associated RNA therapies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

RNA

ISSN

1355-8382

e-ISSN

1469-9001

Svazek periodika

29

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

1379-1387

Kód UT WoS článku

001049266600001

EID výsledku v databázi Scopus

2-s2.0-85168252001