# Mechanism and regulation of Hu family RNA binding proteins during neural alternative polyadenylation

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $591,579

## Abstract

PROJECT ABSTRACT
 3' untranslated regions (3' UTRs) are the hubs of post-transcriptional regulation,
and contain the majority of binding sites for regulatory factors such as miRNAs and RNA
binding proteins (RBPs). Moreover, it has recently become appreciated that most genes
do not express a single 3' UTR, but instead express multiple 3' UTR isoforms through a
process known as alternative polyadenylation (APA). Since APA can be deployed to
coordinately shift the 3' UTR profiles of large cohorts of genes according to tissue
identity, environmental condition, or disease status, APA can broadly affect the post-
transcriptional landscape and profoundly impact gene expression programs.
Nevertheless, very little remains known about the underlying mechanisms of how global
APA programs are enacted. In ongoing work, we identify conserved, redundant roles for
Hu family neural RBPs in driving a broad program of neural 3' UTR lengthening in both
Drosophila and mammalian nervous system. Here, we will use molecular genetic assays
and genomewide analyses to elucidate the mechanism for neural Hu proteins in
conferring neural 3' UTR extensions. Since neural Hu factors have such powerful
capacity to remodel the transcriptome, it may follow that they are under strict control.
Indeed, we have also found that neural Hu genes in both Drosophila and mammals are
subject to unexpectedly complex and strong post-transcriptional suppression outside of
the nervous system. We have developed new genetic models to study these regulatory
mechanisms and their phenotypic impacts, which may reveal new roles for these factors
in developmental patterning and also have tangible implications for a class of human
disease that is caused by misexpression of neural Hu proteins outside of the brain.
Overall, this work will reveal new perspectives on the deployment of the distinctive
neural post-transcriptional landscape and its in vivo biological importance.

## Key facts

- **NIH application ID:** 10328897
- **Project number:** 5R01NS083833-09
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Eric C Lai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $591,579
- **Award type:** 5
- **Project period:** 2014-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328897

## Citation

> US National Institutes of Health, RePORTER application 10328897, Mechanism and regulation of Hu family RNA binding proteins during neural alternative polyadenylation (5R01NS083833-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10328897. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*