The signal peptide of a simple retrovirus envelope functions as a posttranscriptional regulator of viral gene expression.
Retroviruses use different strategies to regulate transcription and translation and exploit the cellular machinery involved in these processes. This study shows that the signal peptide of the envelope glycoprotein (Env) of Jaagsiekte sheep retrovirus (JSRV) plays a major role in posttranscriptional viral gene expression. Expression of the JSRV Env in trans increases viral particle production by mechanisms dependent on (i) its leader sequence, (ii) an intact signal peptide cleavage site, (iii) a cis-acting RNA-responsive element located in the viral genome, (iv) Crm1, and (v) B23. The signal peptide of the JSRV Env (JSE-SP) is 80 amino acid residues in length and contains putative nuclear localization and export signals, in addition to an arginine-rich RNA binding motif. JSE-SP localizes both in the endoplasmic reticulum and in the nucleus, where it colocalizes with nucleolar markers. JSE-SP is a multifunctional protein, as it moderately enhances nuclear export of unspliced viral mRNA and considerably increases viral particle release by favoring a posttranslational step of the replication cycle.
Caporale
Marco
M
Institute of Comparative Medicine, University of Glasgow Faculty of Veterinary Medicine, Glasgow, Scotland.
Arnaud
Frederick
F
Mura
Manuela
M
Golder
Matthew
M
Murgia
Claudio
C
Palmarini
Massimo
M
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D016679:Genome, Viral / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D022141:Jaagsiekte sheep retrovirus / Q000235:genetics / Q000378:metabolism; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D021382:Protein Sorting Signals / Q000235:genetics*; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D000097606:Exportin 1 Protein
D015683:Gene Products, gag; D006023:Glycoproteins; D028884:Karyopherins; D021382:Protein Sorting Signals; D018160:Receptors, Cytoplasmic and Nuclear; D014759:Viral Envelope Proteins; D000097606:Exportin 1 Protein