R01AG078950
Project Grant
Overview
Grant Description
Regulation and Function of dsRNAs Derived from Retrotransposable Elements in AD - Project Summary
The goal of this project is to better understand the regulation and function of RNA derived from retrotransposable elements (RTEs) in Alzheimer's disease (AD), with a focus on double-stranded RNAs (dsRNAs).
RTEs occupy roughly 40% of the human genome. They constitute a major subgroup of transposons, defined as genomic sequences that mobilize using a 'copy-and-paste' mechanism where an RNA intermediate is involved.
To date, most RTEs have lost the ability to mobilize to new locations, at least in normal physiological conditions. However, these elements may still retain regulatory activities through expression of RTE-derived RNAs. This functional aspect is particularly relevant in the human brain, where RTE expression is highest compared to other tissues.
Given the multi-copy nature of each family of RTEs, their transcripts often form dsRNA structures, resulted from repetitive sequence content, bi-directional transcription, or natural sense-antisense transcript pairs.
Numerous studies have shown that aberrant expression of cellular dsRNAs is related to the pathogenesis of various human diseases. Recently, increasing evidence supports the existence of enhanced RNA expression from RTEs in neurodegenerative diseases, including AD. This expression leads to accumulation of dsRNAs in neurons, which is correlated with, for example, loss of nuclear TDP-43 or burden of tau tangles.
As a result of dsRNA accumulation, type I IFN response may be elicited in neurons, which may contribute to AD pathogenesis.
In this project, we aim to determine the identity and origin of AD-relevant dsRNAs derived from RTEs and experimentally validate their functional relevance in neurons. In addition, we will examine the impact of RNA-binding proteins (including ADAR1) on RTE-derived dsRNAs and their functional relevance to AD.
This work will allow a previously unattained level of understanding of the regulation and function of RTE-derived dsRNAs in AD and provide new insights to better understand RTE-related disease mechanisms.
The goal of this project is to better understand the regulation and function of RNA derived from retrotransposable elements (RTEs) in Alzheimer's disease (AD), with a focus on double-stranded RNAs (dsRNAs).
RTEs occupy roughly 40% of the human genome. They constitute a major subgroup of transposons, defined as genomic sequences that mobilize using a 'copy-and-paste' mechanism where an RNA intermediate is involved.
To date, most RTEs have lost the ability to mobilize to new locations, at least in normal physiological conditions. However, these elements may still retain regulatory activities through expression of RTE-derived RNAs. This functional aspect is particularly relevant in the human brain, where RTE expression is highest compared to other tissues.
Given the multi-copy nature of each family of RTEs, their transcripts often form dsRNA structures, resulted from repetitive sequence content, bi-directional transcription, or natural sense-antisense transcript pairs.
Numerous studies have shown that aberrant expression of cellular dsRNAs is related to the pathogenesis of various human diseases. Recently, increasing evidence supports the existence of enhanced RNA expression from RTEs in neurodegenerative diseases, including AD. This expression leads to accumulation of dsRNAs in neurons, which is correlated with, for example, loss of nuclear TDP-43 or burden of tau tangles.
As a result of dsRNA accumulation, type I IFN response may be elicited in neurons, which may contribute to AD pathogenesis.
In this project, we aim to determine the identity and origin of AD-relevant dsRNAs derived from RTEs and experimentally validate their functional relevance in neurons. In addition, we will examine the impact of RNA-binding proteins (including ADAR1) on RTE-derived dsRNAs and their functional relevance to AD.
This work will allow a previously unattained level of understanding of the regulation and function of RTE-derived dsRNAs in AD and provide new insights to better understand RTE-related disease mechanisms.
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Los Angeles,
California
900958349
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 398% from $636,922 to $3,171,872.
Los Angeles University Of California was awarded
AD-RTE dsRNA Regulation and Function Study
Project Grant R01AG078950
worth $3,171,872
from National Institute on Aging in September 2022 with work to be completed primarily in Los Angeles California United States.
The grant
has a duration of 4 years 8 months and
was awarded through assistance program 93.866 Aging Research.
The Project Grant was awarded through grant opportunity Elucidating the Roles of Transposable Elements in AD/ADRD and Aging (R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 6/5/26
Period of Performance
9/1/22
Start Date
5/31/27
End Date
Funding Split
$3.2M
Federal Obligation
$0.0
Non-Federal Obligation
$3.2M
Total Obligated
Activity Timeline
Transaction History
Modifications to R01AG078950
Additional Detail
Award ID FAIN
R01AG078950
SAI Number
R01AG078950-3543213602
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NN00 NIH National Insitute on Aging
Funding Office
75NN00 NIH National Insitute on Aging
Awardee UEI
RN64EPNH8JC6
Awardee CAGE
4B557
Performance District
CA-36
Senators
Dianne Feinstein
Alejandro Padilla
Alejandro Padilla
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute on Aging, National Institutes of Health, Health and Human Services (075-0843) | Health research and training | Grants, subsidies, and contributions (41.0) | $1,273,844 | 100% |
Modified: 6/5/26