Proteoform plasticity modulates the temperature response in circadian timekeeping
- 1Department of Biology, Smith College, Northampton, MA, USA
Abstract
The molecular circadian clock optimally coordinates an organism's physiology with the light/dark cycle. One commonality among circadian molecular clock proteins is that they undergo alternative splicing, yielding multiple proteoforms. The isoform-specific sequences spliced into clock proteins contain intrinsically disordered regions (IDRs), suggesting that these regions might be intricately involved in cellular regulation. However, the functions of these isoform-specific IDRs in the clock remain poorly defined. Here, we use the core clock repressor FREQUENCY (FRQ) from the fungal circadian model system Neurospora crassa to test the hypothesis that alternative splicing of core clock IDRs yields multiple proteoforms that expand the functional regulatory capacity of FRQ. To do so, we biophysically characterized an IDR specific to the long isoform of the core clock repressor FRQ and identified motifs and molecular behaviors that regulate clock robustness in a temperature-dependent manner. We further compared the interactomes of two FRQ isoforms, identifying distinct functions and interacting proteins that could contribute to temperature regulation. Taken together, our data highlight that isoform-specific IDRs in clock-repressor proteins enhance and expand clock function in a context-dependent manner.
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BibTeX
@misc{pelham2026proteoform,
title = {{Proteoform plasticity modulates the temperature response in circadian timekeeping}},
author = {J. F. Pelham and A. T. Keeley and E. T. Usher and J. H. Martinsen and M. S. Jankowski and D. Moses and A. E. Mosier and J. Thomas and N. D. Buckley and B. B. Kragelund and S. Sukenik and A. S. Holehouse and J. M. Hurley},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.05.749499},
url = {https://www.biorxiv.org/content/10.64898/2026.09.05.749499v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Proteoform plasticity modulates the temperature response in circadian timekeeping
AU - J. F. Pelham
AU - A. T. Keeley
AU - E. T. Usher
AU - J. H. Martinsen
AU - M. S. Jankowski
AU - D. Moses
AU - A. E. Mosier
AU - J. Thomas
AU - N. D. Buckley
AU - B. B. Kragelund
AU - S. Sukenik
AU - A. S. Holehouse
AU - J. M. Hurley
PY - 2026
DA - 2026/09/05
PB - bioRxiv
DO - 10.64898/2026.09.05.749499
UR - https://www.biorxiv.org/content/10.64898/2026.09.05.749499v1
AB - The molecular circadian clock optimally coordinates an organism's physiology with the light/dark cycle. One commonality among circadian molecular clock proteins is that they undergo alternative splicing, yielding multiple proteoforms. The isoform-specific sequences spliced into clock proteins contain intrinsically disordered regions (IDRs), suggesting that these regions might be intricately involved in cellular regulation. However, the functions of these isoform-specific IDRs in the clock remain poorly defined. Here, we use the core clock repressor FREQUENCY (FRQ) from the fungal circadian model system Neurospora crassa to test the hypothesis that alternative splicing of core clock IDRs yields multiple proteoforms that expand the functional regulatory capacity of FRQ. To do so, we biophysically characterized an IDR specific to the long isoform of the core clock repressor FRQ and identified motifs and molecular behaviors that regulate clock robustness in a temperature-dependent manner. We further compared the interactomes of two FRQ isoforms, identifying distinct functions and interacting proteins that could contribute to temperature regulation. Taken together, our data highlight that isoform-specific IDRs in clock-repressor proteins enhance and expand clock function in a context-dependent manner.
ER -