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Journal of Virology, June 2001, p. 5567-5575, Vol. 75, No. 12
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.12.5567-5575.2001

Retroviral Constitutive Transport Element Evolved from Cellular TAP(NXF1)-Binding Sequences

Andrei S. Zolotukhin, Daniel Michalowski, Sergey Smulevitch, and Barbara K. Felber*

Human Retrovirus Pathogenesis Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute---Frederick, Frederick, Maryland 21702-1201

Received 23 October 2000/Accepted 14 March 2001

The constitutive transport element (CTE) of type D retroviruses serves as a signal of nuclear export of unspliced viral RNAs. The human TAP(NXF1) protein, a cellular mRNA export factor, directly binds to CTE and mediates nuclear export of CTE-containing RNAs. Here, we use genomic SELEX (systematic evolution of ligands by exponential enrichment) to show that the human genome encodes a family of high-affinity TAP ligands. These TAP-binding elements (TBE) are 15-bp minisatellite repeats that are homologous to the core TAP-binding sites in CTE. The repeats are positioned similarly in the RNA secondary structures of CTE and TBE. Like CTE, TBE is an active nuclear export signal. CTE elements of different species share sequence similarities to TBE in the regions that are neutral for CTE function. This conservation points to a possible common ancestry of the two elements, and in fact, TBE has properties expected from a primordial CTE. Additionally, a molecular fossil of a TBE-like minisatellite is found in the genome of a modern retroelement. These findings constitute direct evidence of an evolutionary link between TBE-related minisatellites and CTE.


* Corresponding author. Mailing address: NCI-FCRDC, Bldg. 535, Rm. 110, Frederick, MD 21702-1201. Phone: (301) 846-5159. Fax: (301) 846-7146. E-mail: felber{at}mail.ncifcrf.gov.


Journal of Virology, June 2001, p. 5567-5575, Vol. 75, No. 12
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.12.5567-5575.2001



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