Recent progress in the research of cold-inducible RNA-binding protein

Abstract

Cold-inducible RNA-binding protein (CIRP) is a cold-shock protein which can be induced after exposure to a moderate cold-shock in different species ranging from amphibians to humans. Expression of CIRP can also be regulated by hypoxia, UV radiation, glucose deprivation, heat stress and H2O2, suggesting that CIRP is a general stress-response protein. In response to stress, CIRP can migrate from the nucleus to the cytoplasm and regulate mRNA stability through its binding site on the 3′-UTR of its targeted mRNAs. Through the regulation of its targets, CIRP has been implicated in multiple cellular process such as cell proliferation, cell survival, circadian modulation, telomere maintenance and tumor formation and progression. In addition, CIRP can also exert its functions by directly interacting with intracellular signaling proteins. Moreover, CIRP can be secreted out of cells. Extracellular CIRP functions as a damage-associated molecular pattern to promote inflammatory responses and plays an important role in both acute and chronic inflammatory diseases. Here, we summarize novel findings of CIRP investigation and hope to provide insights into the role of CIRP in cell biology and diseases.

Extracellular CIRP (eCIRP) and inflammation

“…Cold‐inducible RNA‐binding protein (CIRP) was first described in the late 1990s as an RNA chaperone controlling the expression of cell‐cycle proteins in hibernating animals . Since then, intense research on intracellular CIRP (iCIRP) has revealed its role in the regulation of a variety of cellular stress responses, including mRNA stability, cell proliferation, cell survival, circadian clock gene modulation, telomerase maintenance, stress adaptation, and tumor formation and progression . These iCIRP activities, which allow cells to cope with various cellular stress conditions, have been reviewed in detail .…”

“…Since then, intense research on intracellular CIRP (iCIRP) has revealed its role in the regulation of a variety of cellular stress responses, including mRNA stability, cell proliferation, cell survival, circadian clock gene modulation, telomerase maintenance, stress adaptation, and tumor formation and progression . These iCIRP activities, which allow cells to cope with various cellular stress conditions, have been reviewed in detail . In contrast to iCIRP, extracellular CIRP (eCIRP) was recently discovered to act as a damage‐associated molecular pattern (DAMP) promoting inflammation and injury .…”

Translate the untranslated: excising as a novel post-splicing event

“…CIRBP is an 18-kDa protein that consists of an N-terminal RNA recognition motif (RRM) domain and a C-terminal arginine-glycine rich motif. CIRBP upregulation is observed in various tissues upon mild hypothermia, cold stress, UV radiation, mild hypoxia, and glucose deprivation (13). CIRBP serves its function by binding specific 51 nucleotides-long U-rich motifs in the 3'-untranslated region (3'-UTR) of mRNA transcripts (14,15).…”

Induction of CIRBP expression by cold shock on bovine cumulus–oocyte complexes

“…The exposure to mild hypothermic temperatures induces the expression of cold‐shock proteins (Liao, Tong, Tang, & Wu, ). CIRBP, also called CIRP and A18 hnRNP, is a constitutively expressed cold‐shock protein highly conserved among different species whose expression is present in a large variety of tissues and cells, including the ovaries among others (Zhong & Huang, ). CIRBP is involved in several cellular processes such as cellular proliferation and cell survival, and it is involved in anti‐apoptotic and anti‐senescence pathways (Liao et al., ; Zhong & Huang, ).…”

“…CIRBP, also called CIRP and A18 hnRNP, is a constitutively expressed cold‐shock protein highly conserved among different species whose expression is present in a large variety of tissues and cells, including the ovaries among others (Zhong & Huang, ). CIRBP is involved in several cellular processes such as cellular proliferation and cell survival, and it is involved in anti‐apoptotic and anti‐senescence pathways (Liao et al., ; Zhong & Huang, ). These findings suggest that the induction of CIRBP during in vitro maturation (IVM) of oocytes could improve cryotolerance to vitrification procedures.…”