ZBP2 facilitates binding of ZBP1 to beta-actin mRNA during transcription.
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 beta-actin mRNA localization. ZBP1 colocalizes with nascent beta-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 beta-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 beta-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.
Pan
Feng
F
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
Hüttelmaier
Stefan
S
Singer
Robert H
RH
Gu
Wei
W
D000199:Actins / Q000235:genetics*; D000818:Animals; D030161:Avian Proteins / Q000378:metabolism*; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D016501:Neurites / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011743:Pyrimidines / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
D000199:Actins; D030161:Avian Proteins; C507913:Khsrp protein, mouse; D009687:Nuclear Proteins; D011743:Pyrimidines; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; C498636:ZBP1 protein, Gallus gallus; C446510:ZBP2 protein, Gallus gallus; D012313:RNA