The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases
Shin Yeonoh; Murakami Katsuhiko S; Mäkinen Janne J; Metsä-Ketelä Mikko; Virta Pasi; Vieras Eeva; Belogurov Georgiy A
The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases
Shin Yeonoh
Murakami Katsuhiko S
Mäkinen Janne J
Metsä-Ketelä Mikko
Virta Pasi
Vieras Eeva
Belogurov Georgiy A
NATURE RESEARCH
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042823683
https://urn.fi/URN:NBN:fi-fe2021042823683
Tiivistelmä
RNA polymerases (RNAPs) synthesize RNA from NTPs, whereas DNA polymerases synthesize DNA from 2dNTPs. DNA polymerases select against NTPs by using steric gates to exclude the 2 ' OH, but RNAPs have to employ alternative selection strategies. In single-subunit RNAPs, a conserved Tyr residue discriminates against 2 ' dNTPs, whereas selectivity mechanisms of multi-subunit RNAPs remain hitherto unknown. Here, we show that a conserved Arg residue uses a two-pronged strategy to select against 2 ' dNTPs in multi-subunit RNAPs. The conserved Arg interacts with the 2 ' OH group to promote NTP binding, but selectively inhibits incorporation of 2 ' dNTPs by interacting with their 3 ' OH group to favor the catalytically-inert 2 ' -endo conformation of the deoxyribose moiety. This deformative action is an elegant example of an active selection against a substrate that is a substructure of the correct substrate. Our findings provide important insights into the evolutionary origins of biopolymers and the design of selective inhibitors of viral RNAPs. RNA and DNA polymerases need to discriminate efficiently against closely related nucleotide triphosphate substrates. Here, the authors show that a conserved Arg residue is the major determinant of selectivity against deoxyribonucleoside substrates by multisubunit RNA polymerases.
Kokoelmat
- Rinnakkaistallenteet [19207]