Cold-inducible RNA binding protein (CIRP) expression is modulated by alternative mRNAs.
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 degrees C does not encode for the full-length CIRP open reading frame, while the two major transcripts at 32 degrees C do. Further, the longest transcript detected at 32 degrees 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 degrees 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.
Al-Fageeh
Mohamed B
MB
Protein Science Group, Department of Biosciences, University of Kent, Canterbury, Kent CT27NJ, United Kingdom.|National Centre for Biotechnology, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia
Smales
C Mark
CM
Protein Science Group, Department of Biosciences, University of Kent, Canterbury, Kent CT27NJ, United Kingdom.
D020121:5' Untranslated Regions; D000818:Animals; D003080:Cold Temperature; D051379:Mice; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D020121:5' Untranslated Regions; C106176:Cirbp protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins