Antisense transcription mediated gene expression regulation in Plasmodium falciparum

Abstract

Plasmodium falciparum causes the most severe form of malaria in humans. To complete its life cycle, the parasite undergoes numerous morphological modifications. The parasite is pre-programmed to resist a variety of pressures and can thrive in a variety of settings. Consequently, the pathogenicity of the parasite increases, and antibiotic resistance develops. The underlying biology suggests that gene expression is tightly controlled at the transcriptional, post-transcriptional, and/or translational level. Regulation via epigenetic pathways has also been widely explored. Furthermore, non-coding RNA-mediated gene regulation is a well-studied mechanism, however it is poorly understood in P. falciparum. Stranded RNA sequencing was used to investigate the role of antisense transcription in gene regulation. Antisense transcription has been discovered to be a common occurrence. It is found to be significantly deregulated in stress-induced circumstances, implying that it might play an important function. Antisense RNA, unlike sense RNA, associates with specific proteins, according to our findings. It also makes us think about the control that takes place at the chromatin and translation levels. We developed stable transgenic lines to study the likely mechanism of action. We demonstrate that RNA-RNA duplex formation stabilises RNA and reduces the degradation rates of sense and antisense RNA, resulting in an increase in net quantities. We also show that these duplex RNAs are either not translated or cause ribosomal stalling. We demonstrate antisense and duplex RNA attachment with ribosomes, which increases under stress circumstances. At the same time, we're trying to figure out antisense RNA's non-canonical features. Using a combination of in-silico and in-vitro approaches, we discovered that antisense RNA has coding potential. The validity of peptides synthesized from antisense RNA ORFs, as well as the difference in stress conditions, has been established. We're still attempting to figure out what these peptides do. Our findings are expected to provide light on previously undisclosed aspects of Plasmodium gene regulation. This could help with aspects of translational research and diagnostic innovation in the future.