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Retroviral constitutive transport element evolved from cellular TAP(NXF1)-binding sequences
A S Zolotukhin1, D Michalowski, S Smulevitch
1Human Retrovirus Pathogenesis Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA.
Journal of Virology
|May 18, 2001
Summary
Human cells contain novel RNA export signals called TAP-binding elements (TBEs) that are similar to viral constitutive transport elements (CTEs). These findings reveal an evolutionary link between cellular TBEs and viral CTEs.
Area of Science:
- Molecular Biology
- Virology
- Genomics
Background:
- The constitutive transport element (CTE) of type D retroviruses facilitates nuclear export of unspliced viral RNAs.
- The human TAP (NXF1) protein, a cellular mRNA export factor, binds to CTE and mediates RNA nuclear export.
Purpose of the Study:
- To identify and characterize novel cellular ligands for the human TAP (NXF1) protein.
- To investigate the evolutionary relationship between CTEs and cellular RNA export elements.
Main Methods:
- Genomic SELEX (systematic evolution of ligands by exponential enrichment) was employed to discover high-affinity TAP ligands in the human genome.
- RNA secondary structure analysis and sequence homology comparisons were performed.
Main Results:
- A family of TAP-binding elements (TBEs), consisting of 15-bp minisatellite repeats, were identified as high-affinity TAP ligands.
- TBEs share homology with CTE core binding sites and function as active nuclear export signals, similar to CTEs.
- Sequence similarities between CTEs and TBEs suggest a common ancestry, with TBEs exhibiting properties of a primordial CTE.
Conclusions:
- The human genome encodes TBEs, which are functional nuclear export signals homologous to viral CTEs.
- Evidence suggests an evolutionary link between TBE-related minisatellites and CTEs, supported by conserved sequence elements and functional similarities.
- A molecular fossil of a TBE-like minisatellite in a modern retroelement further supports the evolutionary connection.