# Isoform expression and post-transcriptional regulation of centrosomal plp mRNA

> **NIH NIH K99** · EMORY UNIVERSITY · 2023 · $125,000

## Abstract

PROJECT SUMMARY
Centrosome deregulation is associated with developmental disorders, such as microcephaly, ciliopathy, and
cardiovascular disease. Despite their fundamental importance to human health, relatively little is known
about the regulation of genes encoding core centrosome components, such as Pericentrin (Pcnt)-like protein
(PLP), a conserved centrosome scaffold also required for ciliary function. Completion of this proposal will
advance our understanding of the post- transcriptional regulation of plp mRNA. In humans, deregulation of
the homologous PCNT gene results in congenital diseases, such as microcephalic osteodysplastic
primordial dwarfism type II (MOPD II) and Trisomy 21. Similarly, in Drosophila, plp deregulation leads to
diverse defects, including embryonic lethality, neuron dysfunction, and male sterility. The mechanisms
underlying the pleiotropic phenotypes associated with plp loss are incompletely understood. plp is predicted
to encode 12 mRNA variants, but what mechanisms give rise to these distinct RNA species and how their
expression is spatiotemporally regulated are completely unknown. In this K99/R00 proposal, I will test the
hypothesis that the PLP protein isoform expression, coupled with the post- transcriptional regulation of plp
mRNA, modulates its diverse functions within different tissues. Three aims are proposed to test this
hypothesis. In Aim 1, I will identify mechanisms of embryonic plp mRNA localization and translation. In Aim 2,
I will explore the contribution of alternative promoter and 3’UTR usage for the generation of different plp RNA
variants. In Aim 3, I will determine the expression profile of PLP protein isoforms and examine the biological
function of PLP isoforms, including PLPPM, in Drosophila neuroblasts versus early embryos. The completion
of this work will reveal the mechanisms of spatially and temporally distinct expression patterns of functional
PLP protein isoforms in different Drosophila tissues and will improve our understanding of plp mRNA
regulation, aspects of which may be deregulated in human diseases, such as neurodegenerative disorders
and cardiovascular disease. Moreover, this award will provide technical and professional training in RNA-
sequencing and bioinformatics, CRISPR genome editing, and advanced imaging approaches under the
guidance of my expert mentors. I will follow a structured training program to enhance my professional abilities
to establish and run my own successful independent laboratory.

## Key facts

- **NIH application ID:** 10646408
- **Project number:** 5K99GM143517-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** JUNNAN FANG
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $125,000
- **Award type:** 5
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10646408

## Citation

> US National Institutes of Health, RePORTER application 10646408, Isoform expression and post-transcriptional regulation of centrosomal plp mRNA (5K99GM143517-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10646408. Licensed CC0.

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