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Molecular and Cellular Biology, March 2008, p. 2011-2022, Vol. 28, No. 6
0270-7306/08/$08.00+0     doi:10.1128/MCB.01446-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Translation of cIAP2 mRNA Is Mediated Exclusively by a Stress-Modulated Ribosome Shunt{triangledown}

Kyle W. Sherrill and Richard E. Lloyd*

Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030

Received 10 August 2007/ Returned for modification 21 August 2007/ Accepted 28 December 2007

During cellular stress, translation persists or increases for a number of stress-responsive proteins, including cellular inhibitor of apoptosis 2 (cIAP2). The cIAP2 transcript includes a very long (2.78-kb) 5' untranslated region (UTR) with an unusually high number of upstream AUGs (uAUGs), i.e., 64, and a stable predicted secondary structure ({Delta}G {cong} –620 kcal/mol) that should completely block conventional scanning-dependent translation initiation. This region did not facilitate internal ribosome entry in vitro or when RNA reporter transcripts were transfected into cells. However, several structural features within the cIAP2 5' UTR were observed to be nearly identical to those required for ribosome shunting in cauliflower mosaic virus RNA and are well conserved in cIAP2 orthologs. Selective mutation revealed that the cIAP2 mRNA mediates translation exclusively via ribosome shunting that bypasses 62 uAUGs. In addition, shunting efficiency was altered by stress and was greatly facilitated by a conserved RNA folding domain (1,470 to 1,877 nucleotides upstream) in a region not scanned by shunting ribosomes. This arrangement suggests that regulation of cIAP2 shunting may involve recruitment of RNA binding proteins to modulate the efficiency of translation initiation.

* Corresponding author. Mailing address: Department of Molecular Virology and Microbiology, Rm. 860E, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-8993. Fax: (713) 798-5075. E-mail: rlloyd{at}bcm.edu

{triangledown} Published ahead of print on 14 January 2008.

Molecular and Cellular Biology, March 2008, p. 2011-2022, Vol. 28, No. 6
0270-7306/08/$08.00+0     doi:10.1128/MCB.01446-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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