# Developmental regulation of RNA editing in Trypanosoma brucei

> **NIH NIH F32** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $65,310

## Abstract

Project Summary
 Trypanosoma brucei is a parasitic protozoan and the causative agent of human African trypanosomiasis
in 36 sub-Saharan African countries. The parasite progresses through several, required developmental stages
throughout its life cycle as it transitions between its two hosts, the tsetse fly and mammals. These hosts offer
very different nutritional environments which the parasite must be able to rapidly adapt to and exploit. To
efficiently take advantage of both nutritional environments, T. brucei modulates its mitochondrial activity.
However, while several respiratory subunits are encoded in the mitochondrial genome, most of these
mitochondrial genes do not encode functional open reading frames. To generate translatable open reading
frames, the parasite must post-transcriptionally modify the mRNAs by precise insertion and deletion of often
hundreds of uridine residues in a process termed RNA editing. Concomitant with changing metabolic demands,
editing of several mRNAs is differentially regulated between mammalian long slender bloodstream form (BSF)
and insect vector procyclic form (PCF) parasites, the only stages in which RNA editing has been investigated in
T. brucei. However, the mechanisms by which this regulation takes place and the precise points in the life cycle
when it is triggered are unknown. Recent data call into question older studies regarding which transcripts undergo
developmentally regulated editing, and use of different strains and growth conditions has likely also caused
discrepancies. Our hypothesis is that editing of distinct mRNAs is differentially regulated throughout the T. brucei
life cycle with regard to both timing and mechanism, and that post-translational modification of editing accessory
factors contributes to this regulation. In Aim 1, we will establish a cell line that can transition through both
proliferative and non-proliferative (transmissible) life cycle stages and use qRT-PCR and high throughput
sequencing to define the editing profile of all 12 edited mRNAs in four life cycle stages. Developmentally
regulated accumulation of edited apocytochrome b (CYb) mRNA is well established, and accessory factors
RBP16 and MRP1/2 are required for this accumulation in PCF parasites. In Aim 2, we will test whether arginine
methylation of RBP16 regulates CYb mRNA editing initiation and association of CYb mRNA with the editing
holoenzyme. In Aim 3, we will determine whether the reported developmentally regulated phosphorylation of
MRP1/2 accounts for the ability of this factor to support edited CYb mRNA levels specifically in PCF. This project
builds upon the skills Dr. Smith acquired during his Ph.D. work on protein trafficking in T. brucei. The project will
require him to develop new skills and knowledge, notably in RNA biology, protein-nucleic acid interactions, and
bioinformatics. Dr. Smith will develop professional and academic skills with the help of mentors, and through
courses offered at the University...

## Key facts

- **NIH application ID:** 9991558
- **Project number:** 1F32AI152311-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Joseph Terrell Smith
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991558

## Citation

> US National Institutes of Health, RePORTER application 9991558, Developmental regulation of RNA editing in Trypanosoma brucei (1F32AI152311-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991558. Licensed CC0.

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