# Functional Post-Transcriptional Interplay of the Nuclear RNA Gomafu During Human Neural Cell Development

> **NIH NIH F31** · EMORY UNIVERSITY · 2021 · $46,036

## Abstract

PROJECT SUMMARY
Many cognitive disorders arise from abnormalities at the early stage of brain development. Alternative splicing,
the inclusion or exclusion of specific exons in mRNAs, is a key component in controlling normal neuronal
development but affected in neuropsychiatric diseases represented by schizophrenia (SCZ). Recent discoveries
indicate that long non-coding RNAs (lncRNAs), a class of non-coding RNAs longer than 200 nucleotides which
do not encode for proteins, play sophisticated roles in gene regulation including alternative splicing. IncRNAs
are poorly conserved in general and highly expressed in the human brain. Abnormalities in lncRNA expression
are implicated in neurodegenerative and neuropsychiatric diseases. A particular human lncRNA of interest is
GOMAFU, which is abundantly expressed in human iPSC-derived neural progenitor cells (hNPCs) and brain
neurons but negligible in glia. GOMAFU is a nuclear lncRNA affected in SCZ and known to regulate alternative
splicing of a number of risk factor transcripts involved in SCZ. However, molecular mechanisms regulating
GOMAFU are undefined. Moreover, although GOMAFU was postulated to regulate alternative splicing through
sequestering neuronal RNA-binding protein (RBP) splicing factors, RBPs interacting with GOMAFU still remain
elusive. Emerging evidence, including our preliminary data, indicates that GOMAFU may form a functional
pathway with an RBP called Quaking I (QKI), another SCZ risk factor known to regulate alternative splicing in
neural progenitor cells (NPCs) and neuron-glia lineage development. Recombinant QKI was shown to interact
with GOMAFU in vitro. Furthermore, during development of human iPSC-derived cortical neurons, the decline
of QKI conversely associates with increased GOMAFU expression. Importantly, elimination of QKI leads to
GOMAFU up-regulation in a human NPC cell line. Thus, I hypothesize that QKI-5 suppresses GOMAFU
expression in human NPCs whereas GOMAFU controls splicing in human neuron development through
sequestration of nuclear splicing factors, including QKI-5. The goal of this project is to delineate the function
of the QKI-GOMAFU SCZ risk factor pathway in alternative splicing during human neuronal development. In Aim
1, I will determine whether QKI-5 binds and suppresses GOMAFU biogenesis in a hNPC cell line and human
iPSC-derived NPCs. In Aim 2, I will determine whether GOMAFU regulates QKI nuclear distribution and splicing
function in hNPCs. Moreover, I will utilize the recently developed comprehensive identification of RNA binding
proteins (ChIRP) assay to identify GOMAFU-bound RBP splicing factors and elucidate how GOMAFU modulate
their function in alternative splicing during hNPC development.

## Key facts

- **NIH application ID:** 10314746
- **Project number:** 1F31MH127915-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Paul Michael ZAKUTANSKY
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314746

## Citation

> US National Institutes of Health, RePORTER application 10314746, Functional Post-Transcriptional Interplay of the Nuclear RNA Gomafu During Human Neural Cell Development (1F31MH127915-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10314746. Licensed CC0.

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