# Functional RNA elements in the human genome

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $706,677

## Abstract

Project Summary
This proposal seeks competitive renewal of a multi-PI project (Fu and Yeo), which aims to develop innovative
genomics approaches to elucidate regulatory pathways in the regulation of RNA metabolism. Built upon our
accomplishments in the past funding cycles and aiming at addressing some emerging concepts in regulatory
biology, we propose to pursue four specific aims: In Aim 1, we will develop a novel genomics technology to
measure nascent RNA production at the level of single cells. Once fully developed, we will utilize this
technology to advance the concept of transcription hubs in which genes may be expressed in a coordinated
fashion and link promoters and enhancers within each hub to understand how long-distance regulatory DNA
elements are looped into the proximity of gene promoters to control the amplitude and frequency of burst
transcription. In Aim 2, we will continue the project initiated from the last funding cycle to characterize novel
regulators for alternative polyadneylation (APA). From the proposed genome-wide screen, we have identified 5
gene networks involved in APA regulation, one of which correspond to a group of well-established splicing
factors. We thus propose to pursue the mechanisms underlying the crosstalk between splicing and APA
regulation. In Aim 3, we propose to develop new tethered function assays by constructing a library of ~1000
tethered-enabled RBPs to systematically characterize and identify RBPs involved in APA regulation. Given that
mammalian genomes express several hundred zinc finger-containing proteins that have the capacity to bind
RNA (based in our previous findings) and/or DNA, many of which were also identified from our genome-wide
screens for splicing and APA regulators, we propose to devote Aim 4 to develop a large collection of
genomically tagged cell lines to enable characterization of their transcriptome-wide binding to RNA and/or DNA
and determine their functional impact on gene expression. This proposal combines both hypothesis-driven and
discovery-driven research to address these outstanding problems in the regulation of gene expression.

## Key facts

- **NIH application ID:** 9972640
- **Project number:** 2R01HG004659-13
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Eugene Wei-Ming Yeo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $706,677
- **Award type:** 2
- **Project period:** 2008-06-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972640

## Citation

> US National Institutes of Health, RePORTER application 9972640, Functional RNA elements in the human genome (2R01HG004659-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9972640. Licensed CC0.

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