# Long noncoding RNA function in the Drosophila germ line

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $308,028

## Abstract

Long noncoding RNAs (lncRNAs) were initially defined by a few prominent examples. Application of
high-throughput genomic methods has revealed a dramatically expanded inventory of candidate lncRNAs,
produced in the pervasive transcription of animal genomes. Some lncRNAs are implicated in cancer, and
many others map to regions of the genome suggestive of a link to cancer. Learning how lncRNAs function
thus fits with the overall mission of the NIH. The large number of predicted lncRNAs (over 9000 in humans)
sets up a series of challenges for fully appreciating their functions. An outstanding model for analysis of
lncRNA function is provided by the Drosophila oskar (osk) gene. Although osk RNA encodes a protein, it
also has a noncoding function. The coding and noncoding functions are clearly distinct, acting at different
stages of oogenesis and embryogenesis, and contributing to different processes. The lncRNA function of
osk is essential for progression through oogenesis, and absence of osk RNA results in loss of certain
proteins from nuage, a perinuclear structure found in germ line cells of all animals. Nuage is the site where
piRNAs are produced. piRNAs act in restricting the activity of transposons, thus protecting the germ line
DNA from damage. Notably, loss of osk lncRNA activity leads to a dramatic reduction in piRNA levels, and a
corresponding increase in levels of transposon mRNAs. The goal of this proposal is to understand how osk
RNA acts in nuage organization and piRNA production, features that are conserved among all animals
including humans. One Aim is to complete the genetic characterization of osk mutants and of genes
encoding proteins that bind to the key elements in osk RNA acting in its lncRNA function. One Aim is to
define how nuage is affected by loss of osk RNA, examining individual components to determine if specific
subsets of nuage proteins are primarily affected, and evaluating the overall organization of nuage by
ultrastructural studies. A part of this Aim is to explore and test possible explanations for the requirement that
osk RNA contains signals for transport out of the nurse cells (the cells with nuage) and into the oocyte.
Another Aim centers on the proteins that bind to osk lncRNA functional elements. This builds on our work in
defining these elements, and on identifying the factors that bind to these elements. The goal is to obtain a
more complete understanding of all proteins that bind to the functional elements, to learn about the complex
assembled from these proteins and the osk RNA, and thus to understand the underlying mechanisms. The
final Aim is to search for mammalian equivalents of the critical sequence element that mediates osk lncRNA
activity. Candidates will be tested in mice to determine if this feature plays a conserved role across all
animals, as might be expected given the conservation of nuage, piRNAs, and many nuage components
involved in piRNA production. Collectively, these studies have a high p...

## Key facts

- **NIH application ID:** 9926897
- **Project number:** 5R01GM118526-04
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Paul M. Macdonald
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $308,028
- **Award type:** 5
- **Project period:** 2017-09-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926897

## Citation

> US National Institutes of Health, RePORTER application 9926897, Long noncoding RNA function in the Drosophila germ line (5R01GM118526-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9926897. Licensed CC0.

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