Developmental regulation of edited CYb and COIII mitochondrial mRNAs is achieved by distinct mechanisms in Trypanosoma brucei

0540541 - BC 2021 RIV GB eng J - Journal Article
Smith, J.T. - Doleželová, Eva - Tylec, B. - Bard, J.E. - Chen, R. - Sun, Y. - Zíková, Alena - Read, L. K.
Developmental regulation of edited CYb and COIII mitochondrial mRNAs is achieved by distinct mechanisms in Trypanosoma brucei.
Nucleic Acids Research. Roč. 48, č. 15 (2020), s. 8704-8723. ISSN 0305-1048. E-ISSN 1362-4962
R&D Projects: GA MŠMT(CZ) EF16_019/0000759; GA ČR GA17-22248S
Institutional support: RVO:60077344
Keywords : life-cycle stages * blood-stream form * binding complex * arginine methylation * cis-aconitate * mrb1 complex * differentiation * transcripts * protein * endonuclease
OECD category: Microbiology
Impact factor: 16.971, year: 2020
Method of publishing: Open access
https://academic.oup.com/nar/article/48/15/8704/5879707

Trypanosoma brucei is a parasitic protozoan that undergoes a complex life cycle involving insect and mammalian hosts that present dramatically different nutritional environments. Mitochondrial metabolism and gene expression are highly regulated to accommodate these environmental changes, including regulation of mRNAs that require extensive uridine insertion/deletion (U-indel) editing for their maturation. Here, we use high throughput sequencing and a method for promoting life cycle changes in vitro to assess the mechanisms and timing of developmentally regulated edited mRNA expression. We show that edited CYb mRNA is downregulated in mammalian bloodstream forms (BSF) at the level of editing initiation and/or edited mRNA stability. In contrast, edited COIII mRNAs are depleted in BSF by inhibition of editing progression. We identify cell line-specific differences in the mechanisms abrogating COIII mRNA editing, including the possible utilization of terminator gRNAs that preclude the 3' to 5' progression of editing. By examining the developmental timing of altered mitochondrial mRNA levels, we also reveal transcript-specific developmental checkpoints in epimastigote (EMF), metacyclic (MCF), and BSF. These studies represent the first analysis of the mechanisms governing edited mRNA levels during T. brucei development and the first to interrogate U-indel editing in EMF and MCF life cycle stages.
Permanent Link: http://hdl.handle.net/11104/0318168