# Small RNA regulation of gene expression in Entamoeba

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $623,315

## Abstract

Entamoeba histolytica, a protozoan parasite, is an important human pathogen. Diseases caused by E.
histolytica include dysentery and liver abscesses, and the organism is a leading parasitic cause of death on a
global scale. Regulation of gene expression is a key factor that enables the parasite to adapt to the host
environment during tissue invasion and to convert between life stages to propagate disease outside the host.
One mechanism of gene regulation in Entamoeba is a robust and complex endogenous RNAi pathway. Over
the last several years we have made important observations about this pathway including that amebic small
RNAs have highly unusual 5'-polyP termini and associate with amebic Argonaute 2-2 protein to mediate
transcriptional gene silencing. Additionally, we identified that Entamoeba contains three Argonaute proteins
with different cellular localizations and apparently non-redundant functions. We have also used information on
the amebic RNAi pathway to develop a novel and robust gene-silencing tool in Entamoeba based on use of a
“trigger” gene. Trigger gene silencing is highly robust and stable and is mediated by repressive histone
modifications on the trigger-silenced loci. Our goal is to focus on aspects of RNAi in ameba that are either
unique compared to other systems or which intersect with important aspects of parasite biology. Thus, we will
(i) determine the molecular mechanisms of small RNA “trigger” mediated gene silencing, and (ii)
characterize the components of the Argonaute RNA induced silencing complexes. These data will
improve our understanding of the molecular mechanisms of RNAi in Entamoeba. Our work is at the
intersection of the basic cellular process of RNA-interference and amebic biology. Data that emerge will
contribute to both understanding a basic process in amebic biology and to expanding the knowledge about the
fundamental process of RNAi.

## Key facts

- **NIH application ID:** 9933787
- **Project number:** 5R01AI121084-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** UPINDER SINGH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $623,315
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933787

## Citation

> US National Institutes of Health, RePORTER application 9933787, Small RNA regulation of gene expression in Entamoeba (5R01AI121084-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9933787. Licensed CC0.

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