An assembly of nuclear bodies associates with the active VSG expression site in African trypanosomes

Budzak, James; Jones, Robert E.; Tschudi, Christian; Rudenko, Gloria

doi:10.1038/s41467-021-27625-6

Cited by 22 publications

(41 citation statements)

References 63 publications

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“…In a recent publication, Budzak and others identified three different nuclear bodies associated with the ESB: the Cajal body, the spliced-leader array body (SLAB) and the NUF1P body. They proposed that these bodies facilitate the high requirement for splicing that needs to occur at this site ( Budzak et al, 2022 ).…”

Section: Shared Mechanisms For Mutually Exclusive Expressionmentioning

confidence: 99%

Shared Mechanisms for Mutually Exclusive Expression and Antigenic Variation by Protozoan Parasites

Florini

Visone

Deitsch

2022

Front. Cell Dev. Biol.

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Cellular decision-making at the level of gene expression is a key process in the development and evolution of every organism. Variations in gene expression can lead to phenotypic diversity and the development of subpopulations with adaptive advantages. A prime example is the mutually exclusive activation of a single gene from within a multicopy gene family. In mammals, this ranges from the activation of one of the two immunoglobulin (Ig) alleles to the choice in olfactory sensory neurons of a single odorant receptor (OR) gene from a family of more than 1,000. Similarly, in parasites like Trypanosoma brucei, Giardia lamblia or Plasmodium falciparum, the process of antigenic variation required to escape recognition by the host immune system involves the monoallelic expression of vsg, vsp or var genes, respectively. Despite the importance of this process, understanding how this choice is made remains an enigma. The development of powerful techniques such as single cell RNA-seq and Hi-C has provided new insights into the mechanisms these different systems employ to achieve monoallelic gene expression. Studies utilizing these techniques have shown how the complex interplay between nuclear architecture, physical interactions between chromosomes and different chromatin states lead to single allele expression. Additionally, in several instances it has been observed that high-level expression of a single gene is preceded by a transient state where multiple genes are expressed at a low level. In this review, we will describe and compare the different strategies that organisms have evolved to choose one gene from within a large family and how parasites employ this strategy to ensure survival within their hosts.

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Section: Shared Mechanisms For Mutually Exclusive Expressionmentioning

confidence: 99%

Shared Mechanisms for Mutually Exclusive Expression and Antigenic Variation by Protozoan Parasites

Florini

Visone

Deitsch

2022

Front. Cell Dev. Biol.

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“…However, we are increasingly realising the importance of pre-mRNA processing both in maintaining high levels of VSG expression, as well as its monoallelic control. The two processes of transcription and splicing appear to be interconnected at the active ES, whereby blocking splicing results in strongly reduced processive transcription ( Budzak et al, 2022 ). In this review, we discuss the role of nuclear bodies in facilitating high VSG expression levels.…”

Section: Introductionmentioning

confidence: 99%

“…These nuclear bodies (with the exception of the ESB) are also found in procyclic form T. brucei. The percentage of BF T. brucei cells in G 1 containing one or more of these nuclear bodies is shown in the respective panels [data from ( Budzak et al, 2022 )].…”

Section: Introductionmentioning

confidence: 99%

“…VSG is by far the most abundant mRNA (∼7–10% total) in BF T. brucei . An estimated 666.7 VSG mRNA molecules are generated per hour from a single VSG gene, compared with 1.3 mRNA molecules per hour from a typical Pol II transcribed gene ( Budzak et al, 2022 ) ( Figure 2 ). This staggering 512-fold higher rate of mRNA production, enables generation of the vast amounts of Variant Surface Glycoprotein (VSG) (10 7 molecules, ∼10% total protein) necessary to form a fully protective surface coat ( Bartossek et al, 2017 ; Maudlin et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…For all graphs, the y -axes are the same scale as in panel (A) . Values for mRNA molecules generated per hour were derived from Supplementary Tables 1, 2 in Budzak et al (2022) .…”

Section: Introductionmentioning

confidence: 99%

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Pedal to the Metal: Nuclear Splicing Bodies Turbo-Charge VSG mRNA Production in African Trypanosomes

Budzak

Rudenko

2022

Front. Cell Dev. Biol.

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The African trypanosome Trypanosoma brucei is a parasite of the mammalian bloodstream and tissues, where an antigenically variable Variant Surface Glycoprotein (VSG) coat protects it from immune attack. This dense layer comprised of ∼107 VSG proteins, makes VSG by far the most abundant mRNA (7–10% total) and protein (∼10% total) in the bloodstream form trypanosome. How can such prodigious amounts of VSG be produced from a single VSG gene? Extremely high levels of RNA polymerase I (Pol I) transcription of the active VSG provide part of the explanation. However, recent discoveries highlight the role of pre-mRNA processing, both in maintaining high levels of VSG transcription, as well as its monoallelic expression. Trypanosome mRNAs are matured through trans-splicing a spliced leader (SL) RNA to the 5’ end of precursor transcripts, meaning abundant SL RNA is required throughout the nucleus. However, requirement for SL RNA in the vicinity of the active VSG gene is so intense, that the cell reconfigures its chromatin architecture to facilitate interaction between the SL RNA genes and the active VSG. This presumably ensures that sufficient localised SL RNA is available, and not limiting for VSG mRNA expression. Recently, novel nuclear splicing bodies which appear to provide essential trans-splicing components, have been identified associating with the active VSG. These observations highlight the underappreciated role of pre-mRNA processing in modulating gene expression in trypanosomes. Dissecting the function of these nuclear RNA processing bodies should help us elucidate the mechanisms of both VSG expression and monoallelic exclusion in T. brucei.

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Deviating from the norm: Nuclear organisation in trypanosomes

Field

2023

Current Opinion in Cell Biology

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An assembly of nuclear bodies associates with the active VSG expression site in African trypanosomes

Cited by 22 publications

References 63 publications

Shared Mechanisms for Mutually Exclusive Expression and Antigenic Variation by Protozoan Parasites

Shared Mechanisms for Mutually Exclusive Expression and Antigenic Variation by Protozoan Parasites

Pedal to the Metal: Nuclear Splicing Bodies Turbo-Charge VSG mRNA Production in African Trypanosomes

Deviating from the norm: Nuclear organisation in trypanosomes

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