A nuclear enterprise: zooming in on nuclear organization and gene expression control in the African trypanosome

Abstract

African trypanosomes are early divergent protozoan parasites responsible for high mortality and morbidity as well as a great economic burden among the world's poorest populations. Trypanosomes undergo antigenic variation in their mammalian hosts, a highly sophisticated immune evasion mechanism. Their nuclear organization and mechanisms for gene expression control present several conventional features but also a number of striking differences to the mammalian counterparts. Some of these unorthodox characteristics, such as lack of controlled transcription initiation or enhancer sequences, render their monogenic antigen transcription, which is critical for successful antigenic variation, even more enigmatic. Recent technological developments have advanced our understanding of nuclear organization and gene expression control in trypanosomes, opening novel research avenues. This review is focused on Trypanosoma brucei nuclear organization and how it impacts gene expression, with an emphasis on antigen expression. It highlights several dedicated sub-nuclear bodies that compartmentalize specific functions, whilst outlining similarities and differences to more complex eukaryotes. Notably, understanding the mechanisms underpinning antigen as well as general gene expression control is of great importance, as it might help designing effective control strategies against these organisms.

The endoplasmic reticulum of trypanosomatids: An unrevealed road for chemotherapy

“…The NE has multiple pores that span the inner and outer membranes and are morphologically identical to those found in other eukaryotic cells ( Figure 2C ). ( McConville et al., 2002 ; Faria, 2021 ; Zuma et al., 2021 ). The outer membrane is decorated with ribosomes suggesting that it is a part of o rough ER.…”

Kinetoplastid cell biology and genetics, from the 2020 British Society for Parasitology Trypanosomiasis and Leishmaniasis symposium, Granada, Spain

“…The ESB is a nuclear subcompartment from which the single active variant surface glycoprotein (VSG) is transcribed. Faria discusses many novel and conserved processes within the trypanosome nucleus, emphasising a cohort of highly conserved proteins that are involved in telomeric organisation and hence silencing of VSG expression sites (Faria et al, 2021). Recent work implicates the arrangement of chromatin and the segregation of telomeric regions in trypanosomes, with RAP1, TRF, TIF2 and TelAP1 likely to be involved.…”

“…Writing close to the anniversary of the first UK lockdown on 23 rd March 2020, this is a poignant reminder of those we have lost, but also of resilience in retaining connections, collaborations and advances in our science. Faria (Faria, 2021).…”

“…Boxes highlight features specific to trypanosomes. Modified from an illustration by Joanna Faria (Faria, 2021).

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Nuclear mRNA maturation and mRNA export control: from trypanosomes to opisthokonts

“…The major part of this review will systematically describe and compare nuclear mRNA processing steps of opisthokonts and trypanosomes, with a particular focus on factors and mechanisms that are relevant for mRNA export (see section ‘Nuclear mRNA processing steps in opisthokonts and trypanosomes’). The review will not discuss the spatial organization of part of the RNA processing machinery into nuclear bodies, as this is well covered by another review in this issue (Faria, 2021). The review closes with a discussion on mRNA export control in trypanosomes (see section ‘Co-transcriptional initiation of RNA export indicates the lack of major mRNA export checkpoints in trypanosomes’) and a small outlook.…”