Mammalian regulator of nonsense-mediated rna decay

Details Mammalian regulator of nonsense-mediated rna decay Mammalian regulator of nonsense-mediated rna decay

C - Chemistry, Metallurgy

12

N

C12N 15/52 (2006.01) A01K 67/027 (2006.01) A61K 31/70 (2006.01) A61K 48/00 (2006.01) C12N 9/00 (2006.01) C12N 9/14 (2006.01) C12Q 1/25 (2006.01) C12Q 1/68 (2006.01) G01N 33/573 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2253433

All eukaryotes that have been studied to date possess the ability to detect and degrade transcripts that contain a premature signal for the determination of translation. This process of nonsense-mediated RNA decay (NMRD) has been most comprehensively studied in the yeast Saccharomyces cerevisiae where at least three trans-acting factors (Upf1p through Upf3p) are required. The present invention provides cDNAs encoding human and murine RENT1(<u>re</u>gulator of <u>n</u>onsense <u>t</u>ranscripts). RENT1 is the first identified mammalian protein that contains all of the putative functional elements in Upf1p including zinc finger-like motifs and NTPase domains as well as all motifs common to members of helicase superfamily I. Moreover, expression of a chimeric protein, containing the central region of RENT1 flanked by the extreme N- and C-termini of Upf1p, complements the Upf1p- deficient phenotype in yeast.

Tous les eucaryotes qui ont été étudiés à ce jour possèdent la faculté de déceler et de dégrader les transcrits contenant une signal prématuré de fin de transcription. Ce processus de dégradation de l'ARN induite par des transcrits non-sens a été étudié de manière plus approfondie dans la levure (saccharmocyces cerevisiae) dans laquelle au moins trois facteurs à action trans (Upf1p à Upf3p) sont requis. La présente invention concerne des ADNc codant la protéine RENT1 humaine et murine (régulatrice de transcrits non sens). Rent1 est la première protéine mammifère identifiée qui contienne tous les éléments fonctionnels présumés de Upf1p, y compris les motifs en doigts de zinc et les domaines NTPase, ainsi que tous les motifs communs aux membres de la superfamille hélicase I. En outre, l'expression d'une protéine chimère, contenant la région centrale de la protéine RENT1 flanquée des extrémités N- et C- terminales de UPf1p, complète le phénotype déficient en Upf1p dans la levure.

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