Cold-inducible proteins CIRP and RBM3, a unique couple with activities far beyond the cold.

Xinzhou Zhu,Christoph Bührer,Sven Wellmann

doi:10.1007/s00018-016-2253-7

Abstract

Cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) are two evolutionarily conserved RNA-binding proteins that are transcriptionally upregulated in response to low temperature. Featuring an RNA-recognition motif (RRM) and an arginine–glycine-rich (RGG) domain, these proteins display many similarities and specific disparities in the regulation of numerous molecular and cellular events. The resistance to serum withdrawal, endoplasmic reticulum stress, or other harsh conditions conferred by RBM3 has led to its reputation as a survival gene. Once CIRP protein is released from cells, it appears to bolster inflammation, contributing to poor prognosis in septic patients. A variety of human tumor specimens have been analyzed for CIRP and RBM3 expression. Surprisingly, RBM3 expression was primarily found to be positively associated with the survival of chemotherapy-treated patients, while CIRP expression was inversely linked to patient survival. In this comprehensive review, we summarize the evolutionary conservation of CIRP and RBM3 across species as well as their molecular interactions, cellular functions, and roles in diverse physiological and pathological processes, including circadian rhythm, inflammation, neural plasticity, stem cell properties, and cancer development.

Highlights

Decreased body temperature is a key feature of seasonal hibernation, which is an entrained state of slowed metabolism that widely exists in amphibians and mammals to endure food austerity [1,2,3]
We comprehensively summarized the biological activities of Cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) by elucidating the upstream and downstream molecular and cellular aspects, and highlighting their relationships to various physiological and pathological processes in vivo (Fig. 2)
When studying the various research papers on CIRP and RBM3, a striking observation was the variety of diverse cellular functions in which CIRP and RBM3 are involved

Summary

Introduction

Decreased body temperature is a key feature of seasonal hibernation, which is an entrained state of slowed metabolism that widely exists in amphibians and mammals to endure food austerity [1,2,3]. The two cold-inducible proteins CIRP and RBM3 both function against apoptosis in cultured primary neurons or neuron-like PC12 cells [34, 96, 107]. Similar to the dual role of CIRP in the brain as discussed above, a recent report has shown that hypothermia-induced CIRP expression in the liver protects hepatocytes by reducing ROS production [127], while antiCIRP antibody treatment, which neutralizes secreted CIRP in the serum, significantly decreases the inflammatory response and protects the liver from ischemic-reperfusion injury [128].

Results

Conclusion