# Integrative approach to studying LncRNA functions

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $305,823

## Abstract

Supplementary to the parent R01GM123037 “Integrative approach to studying LncRNA functions”
The recent studies showed that lncRNAs were involved in many neurological diseases such as Alzheimer's
disease (AD). First, lncRNAs impact AD pathogenesis because of their diverse functional effects from the
epigenetic regulation. For example, β-site amyloid precursor protein cleaving enzyme-1 antisense transcript
(BACE1-AS) is the lncRNA transcribed from the opposite strand of β -site APP cleaving enzyme-1 (BACE1)
locus. Cell stress increased BACE1-AS levels, which in turn stimulates BACE1 expression, which could
enhance APP processing and Ab1-42 production. Elevated Ab1-42 levels can further promote BACE1-AS
overexpression and the APP processing cascade in a feedforward manner. Second, accumulating evidence
shows that microRNAs play a critical role in the pathogenesis of AD. From the fact that ~ 90% of the SNPs
associated with diseases are located in non-coding regions and lncRNA plays a role as a sponge of miRNAs,
RNA-level editing, which has the similar effect as the single nucleotide variant in lncRNA, can result in aberrant
gene expression regulation in AD. Third, another pathogenic post-transcriptional modification in lncRNA is the
alternative splicing (AS). 17A mapped in intron 3 of G-protein-coupled receptor 51 gene (GPR51) undergoes
AS. 17A lncRNA is upregulated in AD compared with control and AS event in 17A impairs the GABA B
signaling, enhance Aβ secretion. The role and functions of the known lncRNAs have been accumulated.
However, there is no deep functional annotation of post-transcriptionally modified lncRNAs that have RNA-
editing or alternative splicing events in the AD. Therefore, there is an urgent need to develop new tools for
analyzing the potential functional impact of the post-transcriptionally modified lncRNA systemically in the AD
genome and predict their regulatory mechanisms. Here, we propose to develop an integrated system for
transcriptomic sequencing data-based functional annotation of post-transcriptional modification events of
lncRNAs in AD based on the AD sequencing data from ADSP consortium and other NIH controlled AD data
sets. Our multidisciplinary team proposed the following aims: (1) We will develop functional mechanism
prediction of lncRNAs' RNA-editing events through investigating the gain/loss of the binding sites of miRNAs,
which targeting AD genes (we integrated ~ 1,500 AD genes.), due to RNA-editing with checking the
expressional impact between RNA-editing +/- groups and studying the changed relative energy of lncRNA
secondary structures. (2) We will develop functional mechanism prediction of lncRNAs' AS events through
identifying AD-specific/associated AS events in lncRNAs, correlated lncRNA expressions with AD genes' AS
isoforms, investigating the gain/loss of miRNA binding sites due to AS event, and SNP/SV-induced AS events.
Our study will be focused on AD-related lncRNAs to identify epigenetic impact of thes...

## Key facts

- **NIH application ID:** 10119971
- **Project number:** 3R01GM123037-04S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Xiaobo Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $305,823
- **Award type:** 3
- **Project period:** 2017-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119971

## Citation

> US National Institutes of Health, RePORTER application 10119971, Integrative approach to studying LncRNA functions (3R01GM123037-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10119971. Licensed CC0.

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