Deciphering the RNA Transcription-Export Pathway in Trypanosomes

Technology Overview

Dr. Samson Obado

Trypanosomes, a diverse family of protozoan parasites, are a major source of public health and economic threats around the world. The most well-known trypanosome-caused diseases include African trypanosomiasis, caused by Trypanosoma brucei; American trypanosomiasis or Chagas disease, caused by Trypanosoma cruzi; and leishmaniasis, caused by various Leishmania species. Globally, these three diseases alone affect more than 27 million people and cause an estimated 150,000 deaths every year. In September 2025, Chagas disease was declared endemic in the Southern United States, exemplifying the growing problem of trypanosomes spreading beyond their traditional ranges.

To better understand the inner workings and potential vulnerabilities of these parasitic organisms, biochemist Samson Obado, PhD, is focusing on the trypanosomes’ RNA export pathway, in which messenger RNA (mRNA) transcribed from DNA moves from the cell nucleus to the cytoplasm to become a template for protein translation. Specifically, the Obado Lab is studying the nuclear pore complex (NPC), which is the sole mediator of this mRNA transport between the nucleus and cytoplasm.

Research by Dr. Obado and other scientists has shown that the trypanosome NPC uses vastly different proteins and processes than does its human counterpart for the closely linked steps of transcription and mRNA export. Examining the NPC’s unusual structural and functional relationship to the processing and export pathway could help identify therapeutic targets and clarify how the trypanosome has evolved such a unique complex over time.

Although trypanosomes lack many of the transcription and export components present in vertebrate organisms, they have evolved their own functional counterparts, of which only some have been characterized. Dr. Obado and his collaborators used cell fractionation, green fluorescent protein (GFP) labeling assays, and mass spectrometry to identify 20 distinct proteins as potential components of the NPC. The Obado Lab is further characterizing the proteins using AI programs such as AlphaFold to predict how the proteins fold and interact. The research team then tests its predictions with protein-protein interaction mapping, in which previously identified factors serve as affinity handles for an affinity capture assay developed in the Obado Lab.

Instead of an ATP-dependent helicase that is a standard feature of NPCs in many organisms, for example, trypanosomes use an unusual version of a GTPase protein within the pore to power mRNA export from the nucleus to the cytoplasm. Because the enzyme is radically different from its human counterpart, it represents a potential target for drug development. Perturbation of any component part of the GTPase transport system in trypanosomes results in growth arrest and cell death.

Whereas other single-celled organisms have one mRNA export factor, the Obado Lab’s affinity capture experiments also revealed three distinct export factors in trypanosomes, each with a different role in mRNA export and ribosomal RNA processing. One is a universal factor that is essential for the transport process, the researchers found. The second one has a separate but unclear role in RNA export. The third mRNA export factor is involved in ribosome biogenesis, which is the manufacture of the protein-producing ribosome molecules.

In addition, the Obado Lab is studying the trypanosome NPC using cryo-electron microscopy (cryo-EM) to better understand the distinct morphology of its inner rings, outer rings and the scaffold-like spokes that line the pore. Based on their extensive research, Dr. Obado and his collaborators have shown that the NPC includes species-specific subunit arrangements that are adapted to each organism’s biology. This developing model of transcription and RNA export might help explain the core process in other disease-causing trypanosomes including Plasmodium, the causative agent of malaria.

Dr. Obado has extensive experience with cellular and structural biology tools, protein-mapping assays (e.g., affinity capture, crosslinking mass spectrometry), cryo-EM, and AI protein-folding prediction programs. He has collaborated on multiple investigations of other protein interactions in parasitic, bacterial and human cells. Dr. Obado is interested in further collaborations on investigating the structure and function of NPCs in trypanosomes and on uncovering new RNA export pathways.

Stage of Development

• Preclinical in vitro

Partnering Opportunities

• Collaborative research and development
• Sponsored research agreement
• Data access
• Consultation agreement
• Computational modeling
• High-throughput screening

Learn More

• Samson Obado, PhD
• Obado Lab

Publications

1. Obado SO, Fridy PC, Hegedűsová E, et al. Division of labor in trypanosome RNA processing and export through expanded Mex67 paralogs. Nucleic Acids Res. 2026;54(1):gkaf1443.
2. Butterfield ER, Obado SO, Scutts SR, et al. A lineage-specific protein network at the trypanosome nuclear envelope. Nucleus. 2024;15(1):2310452.
3. Moreira CM, Kelemen CD, Obado SO, et al. Impact of inherent biases built into proteomic techniques: proximity labeling and affinity capture compared. J Biol Chem. 2023;299(1):102726.
4. Obado SO, Rout MP, Field MC. Sending the message: specialized RNA export mechanisms in trypanosomes. Trends Parasitol. 2022;38(10):854-867.
5. Obado SO, Field MC, Rout MP. Comparative interactomics provides evidence for functional specialization of the nuclear pore complex. Nucleus. 2017;8(4):340-352.
6. Obado SO, Brillantes M, Uryu K, et al. Interactome mapping reveals the evolutionary history of the nuclear pore complex. PLoS Biol. 2016;14(2):e1002365.

Last updated October 12, 2026