Cold-inducible RNA binding protein (CIRP) expression is modulated by alternative mRNAs
- Protein Science Group, Department of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom
Abstract
Cold-inducible RNA binding protein (CIRP) is a mammalian protein whose expression is up-regulated in response to mild hypothermia. Although the exact function of this protein is currently unknown, it is thought to function as an RNA chaperone, facilitating mRNA translation upon the perception of cold stress. In this study we have identified and characterized the major CIRP 5′-untranslated region (5′-UTR) transcripts in mouse embryonic fibroblast NIH-3T3 cells. We show that the 5′-UTR of CIRP, a protein highly homologous to the cold-shock protein Rbm3, is much shorter than the previously published 5′ leader sequence of Rbm3. In addition, three major CIRP transcripts with different transcription start sites are generated, with the levels of each of these transcripts being regulated in response to time and temperature. The major transcript generated at 37°C does not encode for the full-length CIRP open reading frame, while the two major transcripts at 32°C do. Further, the longest transcript detected at 32°C shows a discrete expression and stability profile under mild hypothermic conditions and exhibits internal ribosome entry segment (IRES)-like activity. The IRES-like activity is not responsive to conditions of mild hypothermia or hypoxia, but the levels and stability of the transcript harboring the putative IRES are increased at 32°C. We discuss the emerging transcriptional and translational mechanisms by which CIRP expression appears to be controlled and the role that the 5′-UTR plays in the modulation of CIRP expression.
Keywords
- cold-inducible RNA binding protein
- cold shock
- 5′-UTR
- mRNA stability
- alternative transcription start sites
- IRES
Footnotes
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Reprint requests to: C. Mark Smales, Protein Science Group, Department of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom; e-mail: c.m.smales{at}kent.ac.uk; fax: +44 01227 763912.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1179109.
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- Received May 12, 2008.
- Accepted March 11, 2009.
- Copyright © 2009 RNA Society
