Staufen-1 interacts with the human endogenous retrovirus family HERV-K(HML-2) rec and gag proteins and increases virion production.
The human endogenous retrovirus family HERV-K(HML-2) Rec protein is an RNA transport factor that enhances nuclear export of intron-containing retroviral transcripts. Using the yeast two-hybrid approach, we have newly identified human Staufen-1 as a Rec-interacting protein. The interaction was confirmed by coimmunoprecipitation experiments, and the relevant site in Staufen-1 has been mapped to double-stranded RNA binding domain 4 (RBD4). Staufen-1 is in several aspects functionally related to retroviral RNA transport proteins. It binds mRNAs and targets its ribonuclear cargo to polysomes for efficient translation. We observed an accumulation of Staufen-1 in the nucleus of Rec-expressing cells and colocalization in the nucleoli as well as in the cytoplasm. Overexpression of Staufen-1 resulted in a 5-fold enhancement in nuclear export and/or translation of unspliced HERV-K(HML-2) viral RNAs in the presence of Rec and its Rec-responsive element (RcRE) binding site together with a clear increase in virus production. Staufen-1 was previously shown to interact with the Gag protein of HIV-1, promoting Gag oligomerization and RNA encapsidation. We demonstrate here that Staufen-1 also binds to the Gag protein of HERV-K(HML-2). Under stress conditions, Rec colocalizes with Staufen-1 in stress granules in cells that express viral RNA but not in mRNA-decay-related processing bodies. Our results suggest a new role for Staufen-1 as a cellular Rec and HERV-K(HML-2) Gag cofactor.
Division for HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
Kirsten
K
Hanke
Oliver
O
Hohn
Linda
L
Liedgens
Katharina
K
Fiddeke
Jula
J
Wamara
Reinhard
R
Kurth
Norbert
N
Bannert
D001665:Binding Sites; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D020077:Endogenous Retroviruses / Q000502:physiology*; D015683:Gene Products, gag / Q000378:metabolism*; D006801:Humans; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014779:Virus Replication
D003598:Cytoskeletal Proteins; C485839:ERVK-6 protein, human endogenous retrovirus; D015683:Gene Products, gag; D016601:RNA-Binding Proteins; C492185:STAU1 protein, human; D014759:Viral Envelope Proteins