# Function and mechanism of EndoU

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2024 · $376,876

## Abstract

PROJECT SUMMARY
RNA-binding proteins (RBPs), including enzymes that act on RNA, impact all aspects of cellular
function. However, the roles, molecular mechanisms and integration with the cellular regulatory
networks are still unknown for most RBPs. The goal of this study is to elucidate the function,
molecular mechanism, and regulation of a novel endoribonuclease, EndoU. Uniquely, the
RNase activity of EndoU in vitro and in cell culture is directly activated by Ca2+ ions, suggesting
a role in the cellular responses to this key second messenger. Importantly, EndoU misregulation
is associated with uterine, cervical, skin, bronchial, and lung squamous cell cancers. It is heavily
downregulated in esophageal, oral squamous, and cervical cancer, and is a strong prognostic
marker in head/neck and colorectal cancers. EndoU is cytoplasmically expressed in distinct cell
types sharing a major, driving role of programmed cell death in their development: thymocytes,
B cells, squamous epithelial cells, and placental syncytiotrophoblasts. We hypothesize that
EndoU controls survival/differentiation decisions during thymocyte development by cleaving
target RNAs in response to changes in intracellular calcium levels. We specifically aim to fill the
knowledge gap in understanding EndoU’s cellular role, RNA targeting repertoire, and the
mechanism of EndoU activity and its Ca2+-dependent conformational control.

## Key facts

- **NIH application ID:** 10982360
- **Project number:** 1R01GM152548-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** FEDOR V KARGINOV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $376,876
- **Award type:** 1
- **Project period:** 2024-09-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10982360

## Citation

> US National Institutes of Health, RePORTER application 10982360, Function and mechanism of EndoU (1R01GM152548-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10982360. Licensed CC0.

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