# Regulation of microRNA-218 by TRIM9 in Alzheimer's Disease and relhttps://apps.era.nih.gov/gmii/manage/view.era?applId=10497234#ated dementia

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2022 · $381,250

## Abstract

PROJECT SUMMARY
MicroRNAs can inhibit gene expression by binding to mRNAs and prevent them from being translated
into proteins. MicroRNA levels often differ in diseased cells and in healthy cells, leading to differential
expression of certain genes. Controlling microRNA levels therefore offers a promising target for
therapeutic intervention.
MicroRNA-218 (miR-218) is over-expressed in cells obtained from Alzheimer's disease (AD) patients.
Interestingly, we found that miR-218 can be degraded by its target mRNA (TRIM9), which is down-
regulated in Lewy body dementia, an AD-related dementia. This is surprising because microRNAs
usually control the levels of their targets, but not the other way around. This is also exciting because it
is one of the few examples representing a recently discovered gene regulation mode carried out by the
mRNAs and opens up strategies for AD intervention.
In this administrative supplement, we first aim to understand how TRIM9 mRNA triggers miR-218
degradation. Our second aim is to develop an innovative biochemical and computational protocol to
globally identify sequences in different target mRNAs that can induce miRNA degradation in AD patient-
derived cells.
Collectively, our efforts will examine a new mechanism of gene regulation in AD and related dementia,
in which mRNAs counteract microRNAs. Given that we have discovered a potentially widespread
occurrence of the mRNA-induced microRNA degradation pathway, identifying the mRNAs that can
degrade miRNAs would help develop new therapies to combat AD and other types of neurological
diseases.

## Key facts

- **NIH application ID:** 10497234
- **Project number:** 3R35GM128753-05S1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** MINGYI XIE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $381,250
- **Award type:** 3
- **Project period:** 2018-08-13 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497234

## Citation

> US National Institutes of Health, RePORTER application 10497234, Regulation of microRNA-218 by TRIM9 in Alzheimer's Disease and relhttps://apps.era.nih.gov/gmii/manage/view.era?applId=10497234#ated dementia (3R35GM128753-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10497234. Licensed CC0.

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