Posttranscriptional mechanisms controlling diurnal gene expression cycles by body temperature rhythms

Abstract

In mammals, body temperature oscillates in a daily fashion around a set point of 36°C-37°C. These fluctuations are controlled by the circadian master clock residing in the brain's suprachiasmatic nucleus and, despite their small amplitudes, contribute to the diurnal expression of genes throughout the organism. By focusing on the mechanisms underlying the temperature-dependent accumulation of the cold-inducible RNA-binding protein CIRBP - a factor involved in the tuning of amplitude and phase in circadian clocks of peripheral tissues - we have recently identified a novel mechanism governing temperature-dependent gene expression. This mechanism involves the differential spicing efficiency of primary RNA transcripts under different temperature conditions and thereby determines the fraction of Cirbp pre-mRNA processed into mature mRNA. A genome-wide transcriptome analysis revealed that this mechanism affects the output of hundreds of genes. Here we discuss our findings and future directions toward the identification of specific factors and parameters governing temperature-sensitive splicing efficacy.

Effects of Light and Temperature on Daily Activity and Clock Gene Expression in Two Mosquito Disease Vectors

“…Interestingly, temperature cycles may have an even greater influence on the Neurospora clock than the light-dark cycle (Dunlap and Loros, 2017). The mechanism of synchronization with temperature cycles dependent on alternative splicing seems not to be restricted to Neurospora and Drosophila, as it has been found in some mammalian tissues (Gotic and Schibler, 2017). Thus, we believe that future studies focused on the investigation of possible alternative splicing in mosquito clock genes, as well as the analysis of the influence of temperature cycles on the different isoforms, may contribute significantly to our understanding of the clock of these vectors.…”

A Computational Analysis of Alternative Splicing across Mammalian Tissues Reveals Circadian and Ultradian Rhythms in Splicing Events

“…Interestingly, the cold-inducible splicing factor SRSF5 also displayed 24-h rhythmic patterns in transcription in human SW480 cells kept under constant conditions, indicating that its oscillations are not solely due to changes in the internal body temperature of animals. A notable exception to the expected ~12-h shift between oscillations in a diurnal and a nocturnal animal was the cold-inducible hnRNP encoding gene Cirbp : In mouse, Cirbp peaks in the middle of the subjective day, coinciding with a trough in the core body temperature of male C57Bl/6 mice [46], supporting the hypothesis of a temperature-dependent control of Cirbp [47,48]. Yet, the morning peak of expression of CIRBP at ~ZT3 in baboon overlapped with the time at which the body temperature of the animals reached its peak (~37.8 °C) [16], indicating that Cirbp control mechanisms might differ between diurnal and nocturnal mammals.…”

Cirbp-PSD95 Axis Protects Against Hypobaric Hypoxia-Induced Aberrant Morphology of Hippocampal Dendritic Spines and Cognitive Deficits

“…Cirbp as a cell stress molecule senses changes in the external environment including cold, hypoxia, and ultraviolet light and regulates the expression of related molecules in the cell (6). Importantly, Cirbp has been shown to play a positive role in hypothermia-induced neuroprotection (27), sleep homeostasis (28), circadian (29), cardioprotection (7), inflammatory responses of shock and sepsis (30) and neonatal brain injury (31). However, most of the research on Cirbp has focused on its role upon cold exposure, and its function in hypoxia has yet to be delineated.…”