RESUMEN
The human malaria parasite Plasmodium falciparum undergoes a complex life cycle in two hosts, mammalian and mosquito, where it is constantly subjected to environmental changes in nutrients. Epigenetic mechanisms govern transcriptional switches and are essential for parasite persistence and proliferation. Parasites infecting red blood cells are auxotrophic for several nutrients, and mounting evidence suggests that various metabolites act as direct substrates for epigenetic modifications, with their abundance directly relating to changes in parasite gene expression. Here, we review the latest understanding of metabolic changes that alter the histone code resulting in changes to transcriptional programmes in malaria parasites.
Asunto(s)
Malaria Falciparum , Malaria , Animales , Humanos , Cromatina/genética , Plasmodium falciparum/genética , Malaria Falciparum/parasitología , Epigénesis Genética , MamíferosRESUMEN
Various RNA-targeting approaches have been engineered to modify specific sites on endogenous transcripts, breaking new ground for a variety of basic research tools and promising clinical applications in the future. Here, we combine site-directed adenosine-to-inosine RNA editing with chemically induced dimerization. Specifically, we achieve tight and dose-dependent control of the editing reaction with gibberellic acid, and obtain editing yields up to 20 % and 44 % in the endogenous STAT1 and GAPDH transcript in cell culture. Furthermore, the disease-relevant MECP2 R106Q mutation was repaired with editing yields up to 42 %. The introduced principle will enable new applications where temporal or spatiotemporal control of an RNA-targeting mechanism is desired.