Delineation of mRNA export pathways by the use of cell-permeable peptides

Imed Gallouzi, J. A. Steitz

Research output: Contribution to journalArticle

221 Citations (Scopus)

Abstract

The transport of messenger RNAs (mRNAs) from the nucleus to the cytoplasm involves adapter proteins that bind the mRNA as well as receptor proteins that interact with the nuclear pore complex. We demonstrate the utility of cell-permeable peptides designed to interfere with interactions between potential adapter and receptor proteins to define the pathways accessed by particular mRNAs. We show that HuR, a protein implicated in the stabilization of short-lived mRNAs containing AU-rich elements (AREs), serves as an adapter for c-fos mRNA export through two pathways. One involves the HuR shuttling domain, HNS, which exhibits a heat shock-sensitive interaction with transportin 2 (Trn2); the other involves two protein ligands of HuR - pp32 and APRIL - which contain leucine-rich nuclear export signals (NES) recognized by the export receptor CRM 1. Heterokaryon and in situ hybridization experiments reveal that the peptides selectively block the nucleocytoplasmic shuttling of their respective adapter proteins without perturbing the overall cellular distribution of polyadenylated mRNAs.

Original languageEnglish
Pages (from-to)1895-1901
Number of pages7
JournalScience
Volume294
Issue number5548
DOIs
Publication statusPublished - 30 Nov 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)
  • General

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