# Functional analysis of a non-coding RNA in the mammalian circadian clock system

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2020 · $335,290

## Abstract

Circadian rhythmicity is a fundamental aspect of the temporal organization of cells in the body, and it
modulates much of biochemistry, physiology, behavior, and pathological state. Essentially every cell in the
body is capable of generating circadian rhythmicity in mammals, and within each cell, a set of clock genes
(which are highly conserved among animals) form transcription–translation feedback loops that drive circadian
oscillation. Even though the molecular basis of circadian rhythmicity is thought to be well-characterized, recent
transcriptome analyses identified a novel transcript that appears to play an interesting role in these core clock
loops. This transcript, Per2AS, is a natural antisense transcript, a class of non-coding RNAs (ncRNAs), of
Period2 (Per2), one of the core clock genes. Per2AS is transcribed from the strand opposite to Per2 and its
expression is rhythmic and antiphasic to Per2. Given that Per2AS expression is rhythmic and antiphasic to its
sense partner and that rhythmic transcription is more energy-consuming than non-rhythmic transcription, it is
hypothesized that Per2AS is a functional molecule and plays an important role in the mammalian circadian
clock system. Even though ncRNAs were originally considered to be mere transcriptional noise and lack
defined functions, a few dozen examples have expanded the scope of ncRNAs from mere “junk” to functional
molecules having a wide spectrum of regulatory roles. In fact, antisense transcripts of a core clock gene have
been reported in Neurospora crassa and Antheraea pernyi and been shown to confer robust and sustained
rhythmicity, implying that sense-antisense interactions of a core clock gene constitute a common mechanism
for circadian clock regulation across kingdoms. Three specific aims have been designed to test our central
hypothesis and define the biological function of Per2AS in the mammalian circadian clock system. The first aim
addresses whether the presence, rhythmicity, and phase of Per2AS expression relative to Per2 are biologically
significant. The second aim takes advantage of traditional strategies and directly asks whether perturbations of
Per2AS expression result in changes in the circadian clock machinery. The third aim, based on our preliminary
data, focuses on specific molecules that Per2AS may regulate in order to shed light on the molecular
function(s) of Per2AS. Successful completion of this study not only advances our knowledge of circadian
biology but also of regulatory ncRNAs. Only in relatively few cases have interactions between sense and
antisense RNA pairs been explored and the physiological importance and mode-of-action of these pairs remain
poorly understood. Outcomes from the proposed project will have significant impact in understanding the role
of antisense transcripts and shed light on the molecular mechanisms by which antisense transcripts elicit
physiological functions without producing a protein. Deepening the understanding of the clock...

## Key facts

- **NIH application ID:** 10001548
- **Project number:** 5R01GM126223-03
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Shihoko Kojima
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $335,290
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001548

## Citation

> US National Institutes of Health, RePORTER application 10001548, Functional analysis of a non-coding RNA in the mammalian circadian clock system (5R01GM126223-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001548. Licensed CC0.

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