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Cvacka, J.

Publications and source records attributed to Cvacka, J..

2 recordsLinked to original sources

Sweet taste of heavy water

Hydrogen to deuterium isotopic substitution has only a minor effect on physical and chemical properties of water and, as such, is not supposed to influence its neutral taste. Here we conclusively demonstrate that humans are, nevertheless, able to distinguish D2O from H2O by taste. Indeed, highly purified heavy water has a distinctly sweeter taste than same-purity normal water and adds to perceived sweetness of sweeteners. In contrast, mice do not prefer D2O over H2O, indicating that they are not likely to perceive heavy water as sweet. HEK 293T cells transfected with the TAS1R2/TAS1R3 heterodimer and chimeric G-proteins are activated by D2O but not by H2O. Lactisole, which is a known sweetness inhibitor acting via the TAS1R3 monomer of the TAS1R2/TAS1R3, suppresses the sweetness of D2O in human sensory tests, as well as the calcium release elicited by D2O in sweet taste receptor-expressing cells. The present multifaceted experimental study, complemented by homology modelling and molecular dynamics simulations, resolves a long-standing controversy about the taste of heavy water, shows that its sweet taste is mediated by the human TAS1R2/TAS1R3 taste receptor, and opens way to future studies of the detailed mechanism of action. One sentence summaryHeavy water elicits sweet taste for humans via the TAS1R2/TAS1R3 taste receptor.

biochemistry↗

Dinucleoside polyphosphates act as 5'-RNA caps in Escherichia coli

Dinucleoside polyphosphates (NpnNs), discovered more than 50 years ago,1 are pleiotropic molecules present in almost all types of cells.2 It has been shown that their intracellular concentration can under stress conditions increase from the {micro}M to mM range 2,3. However, the cellular roles and mechanisms of action of NpnNs are still speculative4,5. They have never been considered as part of the RNA, even though they have similar chemical structures as already known RNA caps, such as the nicotinamide adenine dinucleotide (NAD)6-8 and 7-methylguanylate cap9. Here, we show that both methylated and non-methylated Npn Ns serve as RNA caps in Escherichia coli (E. coli). NpnNs are excellent substrates for T7 and E. coli RNA polymerases (RNAP) and efficiently initiate transcription. Further, we demonstrate that the E. coli decapping enzyme RNA 5 pyrophosphohydrolase (RppH) is able to remove the NpnNs-cap from the RNA. RppH was, however, not able to cleave the methylated forms of the NpnN-caps, suggesting that the methylation adds an additional layer to the RNA stability regulation. Our work introduces an original perspective on the chemical structure of RNA in prokaryotes and the function of RNA caps. This is the first evidence that small molecules like NpnNs can act in cells via their incorporation into RNA and influence the cellular metabolism.

molecular biology↗