# The role of nuclear pore component Megator in gene expression and dosage compensation

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $45,520

## Abstract

Project Summary
 The goal of this proposal is to determine the role of the nuclear pore complex (NPC) protein Megator
(Mtor) in regulation of gene expression by determining the mechanism via which Mtor influences the epigenetic
phenomenon of dosage compensation in Drosophila melanogaster. Mtor makes up the nuclear basket of the
NPC and appears to form an intranuclear matrix-like structure that, binds along chromatin in post-mitotic,
polytenized salivary gland nuclei. Since Mtor has been implicated in regulation of RNA biogenesis processes in
yeast and in the process of dosage compensation in Drosophila, I examined the effect of Mtor on localization of
a non-coding RNA that is part of the dosage compensation (MSL) complex, roX1. The Drosophila MSL
complex functions to upregulate expression of the single male X chromosome two-fold. Using single molecule
RNA FISH in larval salivary gland nuclei, I detected an increase in nuclear soluble roX1 that is not associated
with the X chromosome in addition to normal roX1 targeting in Mtor-depleted conditions. The increased
presence of nuclear soluble roX1 was found to be due to increased levels of transcription of roX1 in male
nuclei. In addition to rox1, a number of other X-linked genes exhibited a male-specific increase in expression
upon depletion of Mtor, suggesting that normally Mtor functions to restrict dosage compensated gene
expression. Aim 1 will test the hypothesis that Mtor restricts gene expression on the male X chromosome.
RNA- Seq will be performed on larval salivary glands from both control and Mtor depleted conditions as well as
from both males and females. In addition to examining gene expression changes, I will also be able to examine
RNA processing differences by RNA-Seq and RNA FISH in order to begin investigation into the mechanism of
Mtor’s effects on gene expression. Aim 2 will test the hypothesis that Mtor’s effects on gene expression are
dependent on an interaction with components of the MSL complex and of the nuclear exosome, using assays
for chromatin binding and for genetic interactions. These studies will uncover a novel gene regulatory role for a
nuclear-scaffold forming nucleoporin in the context of dosage compensation. These aims will help to elucidate
a role for Mtor in RNA biogenesis in the context of a developing organism as well as expand our understanding
of the NPC’s role in gene regulation.

## Key facts

- **NIH application ID:** 9912636
- **Project number:** 5F31GM133161-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** JENNIFER ALEMAN
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912636

## Citation

> US National Institutes of Health, RePORTER application 9912636, The role of nuclear pore component Megator in gene expression and dosage compensation (5F31GM133161-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9912636. Licensed CC0.

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