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

• Published in: Science (American Association for the Advancement of Science) Vol. 293; no. 5536; pp. 1836 - 1839
• Main Authors: Lykke-Andersen, Jens, Shu, Mei-Di, Steitz, Joan A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 07.09.2001; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: 3' Untranslated Regions - genetics; 3' Untranslated Regions - metabolism; Analysis; Animals; Antibodies; Biological and medical sciences; Biomolecules; Capsid proteins; Cell extracts; Cell Line; Cells; Cellular biology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Exons - genetics; Fundamental and applied biological sciences. Psychology; Fungal Proteins - metabolism; Globins - genetics; HEK293 cells; HeLa Cells; Humans; Introns; Macromolecular Substances; Messenger RNA; Mice; Models, Biological; Molecular and cellular biology; Molecular biology; Molecular genetics; nonsense-mediated decay; Nucleotides; Precipitin Tests; Protein Binding; Proteins; Quality Control; Recombinant Fusion Proteins - metabolism; Ribonucleic acid; Ribonucleoproteins; RNA; RNA Helicases - metabolism; RNA Splicing; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; RNPS1 protein; Saccharomyces cerevisiae Proteins; Splicing; Surveillance; Trans-Activators; Transcription. Transcription factor. Splicing. Rna processing; Transfection; Translation; Degradation; Human; Molecular interaction; Messenger RNA; Splicing
• DOI: 10.1126/science.1062786
• ISSN: 0036-8075

In mammalian cells, splice junctions play a dual role in mRNA quality control: They mediate selective nuclear export of mature mRNA and they serve as a mark for mRNA surveillance, which subjects aberrant mRNAs with premature termination codons to nonsense-mediated decay (NMD). Here, we demonstrate that the protein RNPS1, a component of the postsplicing complex that is deposited 5′ to exon-exon junctions, interacts with the evolutionarily conserved human Upf complex, a central component of NMD. Significantly, RNPS1 triggers NMD when tethered to the 3′ untranslated region of β-globin mRNA, demonstrating its role as a subunit of the postsplicing complex directly involved in mRNA surveillance.