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Molecular and Cellular Biology, December 2007, p. 8340-8351, Vol. 27, No. 23
0270-7306/07/$08.00+0     doi:10.1128/MCB.00972-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

ZBP2 Facilitates Binding of ZBP1 to ß-Actin mRNA during Transcription{triangledown} ,{dagger}

Feng Pan,{ddagger} Stefan Hüttelmaier,§ Robert H. Singer,* and Wei Gu

Department of Anatomy and Structural Biology and Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461

Received 1 June 2007/ Returned for modification 2 July 2007/ Accepted 12 September 2007

Cytoplasmic mRNA localization regulates gene expression by spatially restricting protein translation. Recent evidence has shown that nuclear proteins (such as hnRNPs) are required to form mRNPs capable of cytoplasmic localization. ZBP1 and ZBP2, two hnRNP K homology domain-containing proteins, were previously identified by their binding to the zipcode, the sequence element necessary and sufficient for ß-actin mRNA localization. ZBP1 colocalizes with nascent ß-actin mRNA in the nucleus but is predominantly a cytoplasmic protein. ZBP2, in contrast, is predominantly nuclear. We hypothesized that the two proteins cooperate to localize ß-actin mRNA and sought to address where and how this might occur. We demonstrate that ZBP2, a homologue of the splicing factor KSRP, binds initially to nascent ß-actin transcripts and facilitates the subsequent binding of the shuttling ZBP1. ZBP1 then associates with the RNA throughout the nuclear export and cytoplasmic localization process.

* Corresponding author. Mailing address: Department of Anatomy and Structural Biology and Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: (718) 430-8646. Fax: (718) 430-8697. E-mail: rhsinger{at}aecom.yu.edu

{triangledown} Published ahead of print on 24 September 2007.

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

{ddagger} Present address: Molecular Neurobiology Program, Skirball Institute, New York University Medical Center, New York, NY 10016.

§ Present address: Martin-Luther Universität Halle, ZAMED, Heinrich Damerow Str. 1, 06120 Halle (Saale), Germany.

Molecular and Cellular Biology, December 2007, p. 8340-8351, Vol. 27, No. 23
0270-7306/07/$08.00+0     doi:10.1128/MCB.00972-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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