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Molecular and Cellular Biology, January 2007, p. 368-383, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.00814-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

BiP Internal Ribosomal Entry Site Activity Is Controlled by Heat-Induced Interaction of NSAP1{dagger} ,{triangledown}

Sungchan Cho, Sung Mi Park, Tae Don Kim, Jong Heon Kim, Kyong-Tai Kim, and Sung Key Jang*

NRL, POSTECH Biotech Center, Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea

Received 8 May 2006/ Returned for modification 28 June 2006/ Accepted 4 October 2006

TheBiP protein, a stress response protein, plays an important role in the proper folding and assembly of nascent protein and in the scavenging of misfolded proteins in the endoplasmic reticulum lumen. Translation of BiP is directed by an internal ribosomal entry site (IRES) in the 5' nontranslated region of the BiP mRNA. BiP IRES activity increases when cells are heat stressed. Here we report that NSAP1 specifically enhances the IRES activity of BiP mRNA by interacting with the IRES element. Overexpression of NSAP1 in 293T cells increased the IRES activity of BiP mRNA, whereas knockdown of NSAP1 by small interfering RNA (siRNA) reduced the IRES activity of BiP mRNA. The amount of NSAP1 bound to the BiP IRES increased under heat stress conditions, and the IRES activity of BiP mRNA was increased. Moreover, the increase in BiP IRES activity with heat treatment was not observed in cells lacking NSAP1 after siRNA treatment. BiP mRNAs were redistributed from the heavy polysome to the light polysome in NSAP1 knockdown cells. Together, these data indicate that NSAP1 modulates IRES-dependent translation of BiP mRNA through an RNA-protein interaction under heat stress conditions.


* Corresponding author. Mailing address: PBC, Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea. Phone: 82-54-279-2298. Fax: 82-54-279-8009. E-mail: sungkey{at}postech.ac.kr.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{triangledown} Published ahead of print on 30 October 2006.


Molecular and Cellular Biology, January 2007, p. 368-383, Vol. 27, No. 1
0270-7306/07/$08.00+0     doi:10.1128/MCB.00814-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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