Bacteriophage-related epigenetic natural and non-natural pyrimidine nucleotides and their influence on transcription with T7 RNA polymerase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00600677" target="_blank" >RIV/61388963:_____/24:00600677 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/24:10494953

Výsledek na webu

<a href="https://doi.org/10.1038/s42004-024-01354-5" target="_blank" >https://doi.org/10.1038/s42004-024-01354-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s42004-024-01354-5" target="_blank" >10.1038/s42004-024-01354-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Bacteriophage-related epigenetic natural and non-natural pyrimidine nucleotides and their influence on transcription with T7 RNA polymerase

Popis výsledku v původním jazyce

DNA modifications on pyrimidine nucleobases play diverse roles in biology such as protection of bacteriophage DNA from enzymatic cleavage, however, their role in the regulation of transcription is underexplored. We have designed and synthesized a series of uracil 2ʹ-deoxyribonucleosides and 5ʹ-O-triphosphates (dNTPs) bearing diverse modifications at position 5 of nucleobase, including natural nucleotides occurring in bacteriophages, α-putrescinylthymine, α-glutaminylthymine, 5-dihydroxypentyluracil, and methylated or non-methylated 5-aminomethyluracil, and non-natural 5-sulfanylmethyl- and 5-cyanomethyluracil. The dNTPs bearing basic substituents were moderate to poor substrates for DNA polymerases, but still useful in primer extension synthesis of modified DNA. Together with previously reported epigenetic pyrimidine nucleotides, they were used for the synthesis of diverse DNA templates containing a T7 promoter modified in the sense, antisense or in both strands. A systematic study of the in vitro transcription with T7 RNA polymerase showed a moderate positive effect of most of the uracil modifications in the non-template strand and some either positive or negative influence of modifications in the template strand. The most interesting modification was the non-natural 5-cyanomethyluracil which showed significant positive effect in transcription.

Název v anglickém jazyce

Bacteriophage-related epigenetic natural and non-natural pyrimidine nucleotides and their influence on transcription with T7 RNA polymerase

Popis výsledku anglicky

DNA modifications on pyrimidine nucleobases play diverse roles in biology such as protection of bacteriophage DNA from enzymatic cleavage, however, their role in the regulation of transcription is underexplored. We have designed and synthesized a series of uracil 2ʹ-deoxyribonucleosides and 5ʹ-O-triphosphates (dNTPs) bearing diverse modifications at position 5 of nucleobase, including natural nucleotides occurring in bacteriophages, α-putrescinylthymine, α-glutaminylthymine, 5-dihydroxypentyluracil, and methylated or non-methylated 5-aminomethyluracil, and non-natural 5-sulfanylmethyl- and 5-cyanomethyluracil. The dNTPs bearing basic substituents were moderate to poor substrates for DNA polymerases, but still useful in primer extension synthesis of modified DNA. Together with previously reported epigenetic pyrimidine nucleotides, they were used for the synthesis of diverse DNA templates containing a T7 promoter modified in the sense, antisense or in both strands. A systematic study of the in vitro transcription with T7 RNA polymerase showed a moderate positive effect of most of the uracil modifications in the non-template strand and some either positive or negative influence of modifications in the template strand. The most interesting modification was the non-natural 5-cyanomethyluracil which showed significant positive effect in transcription.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EH22_008%2F0004575" target="_blank" >EH22_008/0004575: RNA pro terapii</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Communications Chemistry

ISSN

2399-3669

e-ISSN

2399-3669

Svazek periodika

7

Číslo periodika v rámci svazku

November

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

256

Kód UT WoS článku

001351596800002

EID výsledku v databázi Scopus

2-s2.0-85209818120