Abstract
The cold inducible RNA binding protein (CIRBP) responds to a wide array of cellular stresses, including short wavelength ultraviolet light (UVC), at the transcriptional and post-translational level. CIRBP can bind the 3'untranslated region of specific transcripts to stabilize them and facilitate their transport to ribosomes for translation. Here we used RNA interference and oligonucleotide microarrays to identify potential downstream targets of CIRBP induced in response to UVC. Twenty eight transcripts were statistically increased in response to UVC and these exhibited a typical UVC response. Only 5 of the 28 UVC-induced transcripts exhibited a CIRBP-dependent pattern of expression. Surprisingly, 3 of the 5 transcripts (IL1B, IL8 and TNFAIP6) encoded proteins important in inflammation with IL-1β apparently contributing to IL8 and TNFAIP6 expression in an autocrine fashion. UVC-induced IL1B expression could be inhibited by pharmacological inhibition of NFκB suggesting that CIRBP was affecting NF-κB signaling as opposed to IL1B mRNA stability directly. Bacterial lipopolysaccharide (LPS) was used as an activator of NF-κB to further study the potential link between CIRBP and NFκB. Transfection of siRNAs against CIRBP reduced the extent of the LPS-induced phosphorylation of IκBα, NF-κB DNA binding activity and IL-1β expression. The present work firmly establishes a novel link between CIRBP and NF-κB signaling in response to agents with diverse modes of action. These results have potential implications for disease states associated with inflammation.
Highlights
Cold-inducible RNA binding protein (CIRBP), known as A18 hnRNP is an 18 kDa protein of the glycine-rich RNA binding protein (GRP) family [1]
We identified IL1B as a transcript that exhibited a CIRBP-dependent pattern of expression following exposure to 254 nm UV (UVC), 290–320 nm UV (UVB), the chemotherapeutic agent cisplatin and bacterial lipopolysaccaride (LPS) but not moderate hypothermia
CIRBP is involved in stress responses Murine CIRBP was cloned from a mouse testis library in a screen to identify RNA binding proteins [1]
Summary
Cold-inducible RNA binding protein (CIRBP), known as A18 hnRNP is an 18 kDa protein of the glycine-rich RNA binding protein (GRP) family [1]. The GRP family of proteins was originally identified in plants but these proteins are conserved from plant to human and they appear to retain many of their functions throughout evolutionary history [4]. Many of these proteins are induced in response to hypothermia and they contribute to cold-tolerance [4]. It was proposed that cold-induced CIRBP inhibited the proliferation of murine fibroblasts, this observation was not supported by recent experiments in CHO cells [9]. CIRBP is widely expressed in tissues that are not exposed to hypothermic conditions so the role of CIRBP in other cellular processes has recently gained attention [10,11]
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