PMID- 9681830 OWN - NLM STAT- MEDLINE DCOM- 19980804 LR - 20061115 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 16 IP - 25 DP - 1998 Jun 25 TI - Nucleocytoplasmic transport of HTLV-1 RNA is regulated by two independent LTR encoded nuclear retention elements. PG - 3309-16 AB - 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. FAU - King, J A AU - King JA AD - Department of Cellular Immunology, German Cancer Research Center, Heidelberg. FAU - Bridger, J M AU - Bridger JM FAU - Lochelt, M AU - Lochelt M FAU - Lichter, P AU - Lichter P FAU - Schulz, T F AU - Schulz TF FAU - Schirrmacher, V AU - Schirrmacher V FAU - Khazaie, K AU - Khazaie K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (RNA, Messenger) RN - 0 (RNA, Viral) RN - 0 (Repressor Proteins) RN - 0 (Ribonucleoprotein, U5 Small Nuclear) SB - IM MH - Animals MH - Biological Transport/genetics/physiology MH - COS Cells MH - Cell Nucleus/chemistry/*metabolism/virology MH - Cells, Cultured MH - Cytoplasm/chemistry/*metabolism/virology MH - Cytoplasmic Streaming/genetics MH - Gene Expression Regulation, Viral MH - HeLa Cells MH - Human T-lymphotropic virus 1/chemistry/*genetics/*metabolism MH - Humans MH - Jurkat Cells MH - RNA Processing, Post-Transcriptional/genetics/physiology MH - RNA, Messenger/metabolism MH - RNA, Viral/*metabolism MH - Repetitive Sequences, Nucleic Acid/*genetics MH - Repressor Proteins/genetics/physiology MH - Ribonucleoprotein, U5 Small Nuclear/genetics/*physiology MH - Transcription, Genetic/genetics/physiology EDAT- 1998/07/29 00:00 MHDA- 1998/07/29 00:01 CRDT- 1998/07/29 00:00 PHST- 1998/07/29 00:00 [pubmed] PHST- 1998/07/29 00:01 [medline] PHST- 1998/07/29 00:00 [entrez] AID - 10.1038/sj.onc.1201884 [doi] PST - ppublish SO - Oncogene. 1998 Jun 25;16(25):3309-16. doi: 10.1038/sj.onc.1201884.