Nature 443, 234-237 (14 September 2006) | doi:10.1038/nature05107; Received 6 May 2006; Accepted 24 July 2006

An intron with a constitutive transport element is retained in a Tap messenger RNA

Ying Li1, Yeou-cherng Bor1, Yukiko Misawa1, Yuming Xue1, David Rekosh1 and Marie-Louise Hammarskjöld1

Alternative splicing is a key factor contributing to genetic diversity and evolution1. Intron retention, one form of alternative splicing, is common in plants2 but rare in higher eukaryotes3, 4, 5, 6, 7, 8, because messenger RNAs with retained introns are subject to cellular restriction at the level of cytoplasmic export and expression9, 10. Often, retention of internal introns restricts the export of these mRNAs and makes them the targets for degradation by the cellular nonsense-mediated decay machinery if they contain premature stop codons11, 12. In fact, many of the database entries for complementary DNAs with retained introns represent them as artefacts that would not affect the proteome11. Retroviruses are important model systems in studies of regulation of RNAs with retained introns, because their genomic and mRNAs contain one or more unspliced introns10. For example, Mason–Pfizer monkey virus overcomes cellular restrictions by using a cis-acting RNA element known as the constitutive transport element (CTE)13. The CTE interacts directly with the Tap protein (also known as nuclear RNA export factor 1, encoded by NXF1), which is thought to be a principal export receptor for cellular mRNA14, leading to the hypothesis that cellular mRNAs with retained introns use cellular CTE equivalents to overcome restrictions to their expression10. Here we show that the Tap gene contains a functional CTE in its alternatively spliced intron 10. Tap mRNA containing this intron is exported to the cytoplasm and is present in polyribosomes. A small Tap protein is encoded by this mRNA and can be detected in human and monkey cells. Our results indicate that Tap regulates expression of its own intron-containing RNA through a CTE-mediated mechanism. Thus, CTEs are likely to be important elements that facilitate efficient expression of mammalian mRNAs with retained introns.

  1. Myles H. Thaler Center for AIDS & Human Retrovirus Research and Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA

Correspondence to: Marie-Louise Hammarskjöld1 Correspondence and requests for materials should be addressed to M.-L.H. (Email: mh7g@virginia.edu).

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