Nucleocytoplasmic transport of HTLV-1 RNA is regulated by two independent LTR encoded nuclear retention elements

Jason A. King, Joanna M. Bridger, Martin Löchelt, Peter Lichter, Thomas F. Schulz, Volker Schirrmacher, Khashayarsha Khazaie

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Appropriate expression of HTLV-1 genes requires transcriptional transactivation by Tax and post-transcriptional regulation by Rex, both mediated by LTR encoded RNA sequences. Using a combination of deletion mutagenesis, Rex-reporter CAT assays, fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy it was established that in the absence of Rex, CAT mRNAs harboring HTLV-1 LTR sequences were unable to leave the nucleus. Deletion of the known U5 encoded cis-acting repressing sequence (CRS) led to a partial release of nuclear retention. A novel regulatory element overlapping the 3' Rex responsive element (RxRE) region was shown to prevent export and expression of these transcripts. Deletion of both the 5' LTR encoded CRS and 3' LTR encoded downstream repressive sequence (3' CRS) led to constitutive mRNA nuclear export and gene expression, independently of Rex. The locations of the two regulatory elements indicate that while the 5' CRS selectively acts to hinder export of unspliced transcripts, the 3' CRS has the capacity to induce nuclear retention of all HTLV-1 transcripts, and therefore could potentially contribute to viral latency in infected cells.

Original languageEnglish (US)
Pages (from-to)3309-3316
Number of pages8
JournalOncogene
Volume16
Issue number25
DOIs
StatePublished - Jun 25 1998

Keywords

  • CRS
  • HTLV-1
  • Nuclear export
  • RxRE

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    King, J. A., Bridger, J. M., Löchelt, M., Lichter, P., Schulz, T. F., Schirrmacher, V., & Khazaie, K. (1998). Nucleocytoplasmic transport of HTLV-1 RNA is regulated by two independent LTR encoded nuclear retention elements. Oncogene, 16(25), 3309-3316. https://doi.org/10.1038/sj.onc.1201884