# The basic functions of Trypanosoma brucei's two introns

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2020 · $246,000

## Abstract

Summary/Abstract
 Kinetoplastid organisms include the parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania
spp. which cause the neglected tropical human diseases Sleeping Sickness (aka Human African
Trypanosomiasis), Chagas’ disease, and Leishmaniasis, respectively. A common feature of these parasites is
their streamlined genomes. Protein-coding genes are arranged in dense directional arrays in which the reading
frames are typically separated by only a few hundred base pairs. In addition, these genes have undisrupted
reading frames, e.g. do not encode introns. Transcriptome studies determined that the genome of T. brucei
harbors only two introns. One intron disrupts the PAP1 gene which encodes a specialized poly(A) polymerase
that is involved in the maturation of small nucleolar (sno)RNAs. snoRNAs are essential for ribosome
biogenesis, guiding processing and post-transcriptional modification of ribosomal RNA. The second intron is
located in the DPB2B gene which encodes a DEAD box RNA helicase. While such helicases are important
factors in several molecular processes including transcription, RNA splicing and ribosome biogenesis, the
specific function of DBP2B is not yet known. We found that all kinetoplastids analyzed, including the distantly
related Bodo saltans, encode PAP1 and DBP2B orthologs with the intron present in a conserved position,
disrupting the same codon in each gene. Since it is generally accepted that all branches of extant eukaryotes
originated from intron-rich progenitors, the question arises why these introns have been conserved over an
estimated 500 million years of evolutionary time in kinetoplastids and have not been eliminated as other
introns. We predict that the introns are fundamentally important, preventing kinetoplastids, free-living or
parasitic, to eliminate them from their genes. We will investigate the basic roles of the two introns by an array
of genetic manipulations. Preliminary data suggest that the PAP1 intron negatively impacts the expression of
its gene, raising the possibility that uncontrolled or overexpression of this gene affects parasite fitness. For
DBP2B we also strive to understand the helicase’s specific function which will be important in evaluating the
intron’s regulatory role. Given the fact that we could not find a kinetoplastid genome without the genes and
introns present, this project may [eventually] provide an intervention target against which it will be difficult for
the parasites to develop resistance.

## Key facts

- **NIH application ID:** 9823856
- **Project number:** 5R21AI142149-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** ARTHUR GUNZL
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $246,000
- **Award type:** 5
- **Project period:** 2018-11-16 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9823856

## Citation

> US National Institutes of Health, RePORTER application 9823856, The basic functions of Trypanosoma brucei's two introns (5R21AI142149-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9823856. Licensed CC0.

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