The cell surface of bloodstream form African trypanosomes is covered by a dense coat of immunogenic variant surface glycoproteins (VSGs). By continuously changing the expressed VSG antigen, the parasites can survive the host’s immune response. The VSG is highly expressed in Trypanosoma brucei, accounting for approximately 10 – 20% of total mRNA. Depletion of VSG mRNA is lethal, and a counterbalancing of the mRNA levels occurs when two or more VSGs are simultaneously expressed. How the VSG expression levels are regulated is unknown. Here, by using inducible and constitutive systems for ectopic VSG expression, we have discovered that (i) the endogenous VSG mRNA level is downregulated only when the ectopic VSG is targeted to the ER, (ii) VSG translation is dispensable and in fact, (iii) the regulation of VSG mRNA levels does not depend on a VSG open reading frame. We propose that feedback elicited at the ER regulates the VSG mRNA amounts to avoid overshooting the secretory pathway capacity. In this way, VSG expression is quantitatively and qualitatively fine-tuned. Balancing the overall number of ER-targeted mRNAs could well be a general mechanism in cell biology. The trypanosome system with just one dominant mRNA species provides a versatile model for studying this phenomenon.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.