Translational regulation in blood stages of the malaria parasite Plasmodium spp.: systems‐wide studies pave the way

Abstract

The malaria parasite Plasmodium spp. varies the expression profile of its genes depending on the host it resides in and its developmental stage. Virtually all messenger RNA (mRNA) is expressed in a monocistronic manner, with transcriptional activation regulated at the epigenetic level and by specialized transcription factors. Furthermore, recent systems‐wide studies have identified distinct mechanisms of post‐transcriptional and translational control at various points of the parasite lifecycle. Taken together, it is evident that ‘just‐in‐time’ transcription and translation strategies coexist and coordinate protein expression during Plasmodium development, some of which we review here. In particular, we discuss global and specific mechanisms that control protein translation in blood stages of the human malaria parasite Plasmodium falciparum, once a cytoplasmic mRNA has been generated, and its crosstalk with mRNA decay and storage. We also focus on the widespread translational delay observed during the 48‐hour blood stage lifecycle of P. falciparum—for over 30% of transcribed genes, including virulence factors required to invade erythrocytes—and its regulation by cis‐elements in the mRNA, RNA‐processing enzymes and RNA‐binding proteins; the first‐characterized amongst these are the DNA‐ and RNA‐binding Alba proteins. More generally, we conclude that translational regulation is an emerging research field in malaria parasites and propose that its elucidation will not only shed light on the complex developmental program of this parasite, but may also reveal mechanisms contributing to drug resistance and define new targets for malaria intervention strategies. WIREs RNA 2016, 7:772–792. doi: 10.1002/wrna.1365For further resources related to this article, please visit the WIREs website.

Evidence of non-tandemly repeated rDNAs and their intragenomic heterogeneity inRhizophagus irregularis

“…Such a complete lack of rDNA tandem repeats have never been detected in wild or artificial eukaryote except malaria-causing Plasmodium parasites 55,56 . The rDNA polymorph was also confirmed in Plasmodium 55,56 .…”

“…Such a complete lack of rDNA tandem repeats have never been detected in wild or artificial eukaryote except malaria-causing Plasmodium parasites 55,56 . The rDNA polymorph was also confirmed in Plasmodium 55,56 . Our results on a fungus evolutionary distinct from Plasmodium (Alveolata) and Arabidopsis (Archaeplastida) reinforce the generality of the hypothesis that rDNA homogeneity depends on its tandem repeat structure.…”

“…yeast, mice, and Arabidopsis), RNA editing and switching of ribosomal protein paralogs produces heterogeneous ribosomes and subsequently alters phenotypes 62 . Furthermore, the malaria parasite with heterogeneous rDNA also produces functionally different multiple rRNA and changes the expression level of each paralog depending on the host species (mammalian or insects) 56,62 . AMF is like the malaria parasite in that they both infect distantly related host species.…”

Messenger RNAs with large numbers of upstream ORFs are translated via leaky scanning and reinitiation in the asexual stages ofPlasmodium falciparum

“…Interestingly, transcript and protein levels during each stage of the parasite's lifecycle are poorly correlated which points towards translationally controlled expression (Le Roch et al, 2004) and a translational regulator, PfALBA1, represses translation of transcripts involved in invasion until the parasite is mature enough to invade (Vembar et al, 2015(Vembar et al, , 2016.…”

Single Cell RNA-sequencing reveals cellular heterogeneity, stage transition and antigenic variation during stress adaptation in synchronized Plasmodium falciparum

“…Plasmodium is known to have tight gene regulation orchestrated at multiple levels by chromatin structure [16,17], transcription [18][19][20] and translation [21,22], which helps in timely expression of different genes required at various stages of parasite growth [23]. Despite tight-gene regulation there is a huge amount of transcriptional heterogeneity exists in the parasite populations [3].…”