Epstein-Barr virus protein EB2 contains an N-terminal transferable nuclear export signal that promotes nucleocytoplasmic export by directly binding TAP/NXF1.
The Epstein-Barr virus early protein EB2 (also called BMLF1, Mta, or SM), which allows the nuclear export of a subset of early and late viral mRNAs derived from intronless genes, is essential for the production of infectious virions. An important feature of mRNA export factors is their capacity to shuttle continuously between the nucleus and the cytoplasm. In a previous study, we identified a novel CRM1-independent transferable nuclear export signal (NES) at the N terminus of EB2, between amino acids 61 and 146. Here we show that this NES contains several small arginine-rich domains that cooperate to allow efficient interaction with TAP/NXF1. Recruitment of TAP/NXF1 correlates with this NES-mediated efficient nuclear export when it is fused to a heterologous protein. Moreover, the NES can export mRNAs bearing MS2 RNA-binding sites from the nucleus when tethered to the RNA via the MS2 phage coat protein RNA-binding domain.
Unité de Virologie Humaine, INSERM U758, ENS-Lyon, 46 allée d'Italie, 69364 Lyon, Cedex 07, France.
Franceline
F
Juillard
Edwige
E
Hiriart
Nicolas
N
Sergeant
Valérie
V
Vingtdeux-Didier
Hervé
H
Drobecq
Alain
A
Sergeant
Evelyne
E
Manet
Henri
H
Gruffat
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D049790:Nuclear Export Signals; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*
C122111:NXF1 protein, human; D049790:Nuclear Export Signals; D029543:Nucleocytoplasmic Transport Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C090236:SM protein, Human herpesvirus 4; D015534:Trans-Activators