Communication of the Position of Exon-Exon Junctions to the mRNA Surveillance Machinery by the Protein RNPS1

doi:10.1126/science.1062786

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Science 7 September 2001:
Vol. 293. no. 5536, pp. 1836 - 1839
DOI: 10.1126/science.1062786

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Communication of the Position of Exon-Exon Junctions to the mRNA Surveillance Machinery by the Protein RNPS1

Jens Lykke-Andersen,^* Mei-Di Shu, Joan A. Steitz

In mammalian cells, splice junctions play a dual role in mRNA quality control: They mediate selective nuclear export of maturemRNA and they serve as a mark for mRNA surveillance, which subjectsaberrant mRNAs with premature termination codons to nonsense-mediateddecay (NMD). Here, we demonstrate that the protein RNPS1, a componentof the postsplicing complex that is deposited 5' to exon-exonjunctions, interacts with the evolutionarily conserved human Upfcomplex, a central component of NMD. Significantly, RNPS1 triggersNMD when tethered to the 3' untranslated region of $beta$ -globin mRNA,demonstrating its role as a subunit of the postsplicing complexdirectly involved in mRNA surveillance.

Howard Hughes Medical Institute, Molecular Biochemistry and Biophysics, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
^* Present address: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347,USA.

To whom correspondence should be addressed: E-mail: joan.steitz{at}yale.edu.