# Identifying Critical Interactions in the Unique Trypanosoma brucei 5S Ribonucleoprotein Complex and their Role in Ribosome Biogenesis

> **NIH NIH F30** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $50,520

## Abstract

ABSTRACT
Trypanosoma brucei is a eukaryotic parasite responsible for the disease Human African Trypanosomiasis (HAT),
which has an at-risk population of 70 million. HAT is nearly always fatal without treatment, but current
medications are expensive, difficult to administer, and rife with adverse side effects. Therefore, there is a need
for the development of new drugs. One approach to which is targeting processes that are both essential for
parasite survival and pathogen-specific. Ribosome biogenesis is the process of assembling numerous protein
and ribosomal RNA components into mature, functional ribosomes. One critical process of ribosome biogenesis
is the formation and incorporation of the 5S ribonucleoprotein (RNP) complex into developing 60S ribosomal
subunits. Recent high resolution cryo-electron microscopy structures have identified key inter- and intra-subunit
interactions between members of the 5S RNP complex and the 60S subunit, which lead to conformational shifts
in protein and RNA components of the ribosome. Therefore, the incorporation of the 5S RNP acts as a crucial
regulatory checkpoint, with disruption of the process resulting in cessation of ribosome maturation at the level of
the 60S subunit. Given that functional ribosomes are required for survival, this makes the assembly and
incorporation of the 5S RNP complex a promising target for future drug development. Work in our laboratory has
identified the trypanosome-specific proteins P34/P37 as a unique and essential part of the T. brucei 5S RNP.
We have also shown direct and unique in vitro interactions between P34/P37 and the protein L5 and 5S rRNA,
two well-studied components of the 5S RNP. Recently, we identified T. brucei homologues of the proteins L11,
Rpf2 and Rrs1, which are involved in maturation and incorporation of the 5S RNP in yeast. We hypothesize
that these homologues form a network of interactions between homologous and unique components of
the 5S RNP complex, and are crucial for its formation and incorporation. The specific aims that will be the
focus of this project are the following:
1) To characterize the interactions between the T. brucei homologues of L11, Rpf2/Rrs1 and other
homologous and unique components of the 5S RNP complex using in vitro studies.
2) Determine the in vivo importance of L11 and Rpf2/Rrs1 in ribosome biogenesis using RNAi knock-
down cell lines.
HAT remains a significant disease burden on populations in many sub-Saharan African countries, in part due to
the many problems associated with current treatments. Using small molecules to target the unique proteins
P34/P37 and their essential role as members of the 5S RNP complex is a potential path to developing new
treatments to combat HAT. Therefore, characterizing the network of interactions occurring between
members of the 5S RNP complex in T. brucei will set a future path toward the development of small
molecule chemotherapeutics as novel treatments for HAT.

## Key facts

- **NIH application ID:** 9971560
- **Project number:** 5F30GM125117-04
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Daniel Jaremko
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-07-19 → 2021-07-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971560

## Citation

> US National Institutes of Health, RePORTER application 9971560, Identifying Critical Interactions in the Unique Trypanosoma brucei 5S Ribonucleoprotein Complex and their Role in Ribosome Biogenesis (5F30GM125117-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971560. Licensed CC0.

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