Circadian rhythms are a roughly 24-hour cycle in the biochemical, physiological or behavioral processes of living entities and are present from animals to cyanobacteria. A circadian rhythm is defined as a cycle that has a period of about a single day, can persist in the absence of time cues while retaining the ability to be reset by them, and is not affected by signals outside these cues. The proteins that constitute the core components of the Neurospora clock, one of the best-studied circadian systems, include Frequency (FRQ), White Collar 1 (WC-1), White Collar 2 (WC-2) and Frequency Interacting RNA Helicase (FRH). While the first three components are well studied, many questions remain about the role that FRH plays in the function of the Neurospora clock.
The aim of this work is to identify the function of FRH in the Neurospora circadian clock. To investigate this mechanism, I will use a multi-facetted approach.
In Specific Aim 1, I will identify the regions of FRH that are essential to cellular growth and development, and distinguish them from regions that are related to the function of the circadian clock using the FRHR806H strain;a strain in which the rhythmicity of the clock is knocked out while maintaining the health of the strain.
In Specific Aim 2, to further understand the function and importance of FRH, I will look at the interactions between the other core components and FRH, while identifying the regions of FRH important for each interaction.
In Specific Aim 3, I will determine the RNA targets of FRH and explore its role as an mRNA interacting protein, a function that is suggested by its homology to the DEAD box family of proteins, in particular the DSHCT family. Because of its similarity to DEAD-box proteins it is logical to assert that FRH may facilitate the interaction of clock controlled gene mRNAs with necessary partners. This would demonstrate an entirely new level of control in the circadian system. Given the many and strong similarities between fungal and animal clocks, specifically including the conservation of regulatory architecture and components, understanding the function of a new family of proteins involved at the core of the circadian rhythm broadens the horizons of how we understand the clock mechanism. Identifying the specific role of this new player will tease out yet another level of awareness as to the sensitivity and response of the clock. Since the Neurospora clock is often used to understand the human clock, this could give us greater insight into our cycle and all of the implications that are associated with it, from ecology to human disease.
Given the many and strong similarities between fungal and animal clocks, understanding the function of a new family of proteins involved at the core of the circadian rhythm broadens the horizons of how we understand the clock mechanism (1). The effectiveness of medical treatment, sleep disorders, psychiatric disorders, cardiovascular disease, and cancer have all been linked to the rhythm of the circadian clock (2-6). Since the Neurospora clock is often used to understand the human clock, this could give us greater insight into our cycle and all of the implications that are associated with it.
|Hurley, Jennifer M; Larrondo, Luis F; Loros, Jennifer J et al. (2013) Conserved RNA helicase FRH acts nonenzymatically to support the intrinsically disordered neurospora clock protein FRQ. Mol Cell 52:832-43|
|Hurley, Jennifer M; Chen, Chen-Hui; Loros, Jennifer J et al. (2012) Light-inducible system for tunable protein expression in Neurospora crassa. G3 (Bethesda) 2:1207-12|