Anti-idiotype RNAs that mimic the leucine-rich nuclear export signal and specifically bind to CRM1/exportin 1

Jörg Hamm*, Maarten Fornerod

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

Background:
Anti-idiotype approaches are based on the assumption that an antibody recognising a ligand can be structurally related to the receptor. Recently we have generated anti-idiotype RNA aptamers designed to mimic the human immunodeficiency virus-1 (HIV-1) Rev nuclear export signal (NES). Nuclear injection of either NES-peptide conjugates or aptamer causes the inhibition of Rev-mediated export. This implied that NES mimics and export substrate might compete for binding to the NES receptor. The mechanism of inhibition, however, is unknown.

Results:
The interaction between the export aptamer and CRM1 was characterised in vitro. The aptamer binds specifically to CRM1 and this interaction is sensitive to competition by Rev NES-peptide conjugates. The recognition domain of CRM1 has been mapped and includes residues found previously to affect binding of leptomycin B, a fungicide interfering with nuclear export.

Conclusions:
Inhibition of Rev-mediated export in vivo by export aptamers appears to result from the binding of the aptamers to the NES-recognition domain of CRM 1. This observation demonstrates that anti-idiotype RNA can mimic faithfully structural and functional properties of a protein and can be used to map ligand-binding domains of receptors.

Original languageEnglish
Pages (from-to)345-354
Number of pages10
JournalChemistry and Biology
Volume7
Issue number5
DOIs
Publication statusPublished - 1 May 2000
Externally publishedYes

Bibliographical note

© 2000 Elsevier Science Ltd. All rights reserved.

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