Evidence of efficient stop codon readthrough in four mammalian genes

作者: Gary Loughran , Ming-Yuan Chou , Ivaylo P. Ivanov , Irwin Jungreis , Manolis Kellis

DOI: 10.1093/NAR/GKU608

关键词:

摘要: Stop codon readthrough is used extensively by viruses to expand their gene expression. Until recent discoveries in Drosophila, only a very limited number of cases chromosomal genes had been reported. Analysis conserved protein coding signatures that extend beyond annotated stop codons identified potential four mammalian genes. Here we use modified targeted bioinformatic approach identify further three candidates. All seven were tested experimentally using reporter constructs transfected into HEK-293T cells. Four displayed efficient readthrough, and these have UGA immediately followed CUAG. Comparative genomic analysis revealed the candidates containing UGA-CUAG, this motif not mammals but throughout vertebrates with first six nucleotides being universally conserved. The importance CUAG was confirmed systematic mutagenesis approach. One gene, OPRL1, encoding an opiate receptor, extremely levels (∼31%) Signals both 5 � 3 OPRL1

参考文章(66)
Kim M. Keeling, David M. Bedwell, Recoding Therapies for Genetic Diseases Springer, New York, NY. pp. 123- 146 ,(2010) , 10.1007/978-0-387-89382-2_6
Alexander S Mankin, Susan W Liebman, Baby, don't stop! Nature Genetics. ,vol. 23, pp. 8- 10 ,(1999) , 10.1038/12600
A. Björnsson, S. Mottagui-Tabar, L. A. Isaksson, Structure of the C-terminal end of the nascent peptide influences translation termination. The EMBO Journal. ,vol. 15, pp. 1696- 1704 ,(1996) , 10.1002/J.1460-2075.1996.TB00515.X
Heather L. True, Susan L. Lindquist, A yeast prion provides a mechanism for genetic variation and phenotypic diversity Nature. ,vol. 407, pp. 477- 483 ,(2000) , 10.1038/35035005
Warren P. Tate, Elizabeth S. Poole, Sally A. Mannering, Hidden Infidelities of the Translational Stop Signal Progress in Nucleic Acid Research and Molecular Biology. ,vol. 52, pp. 293- 335 ,(1996) , 10.1016/S0079-6603(08)60970-8
Olivier Namy, Guillemette Duchateau-Nguyen, Jean-Pierre Rousset, Translational readthrough of the PDE2 stop codon modulates cAMP levels in Saccharomyces cerevisiae Molecular Microbiology. ,vol. 43, pp. 641- 652 ,(2002) , 10.1046/J.1365-2958.2002.02770.X
Hildburg Beier, Miroslawa Barciszewska, Guido Krupp, Rita Mitnacht, Hans J. Gross, UAG readthrough during TMV RNA translation: isolation and sequence of two tRNAsTyr with suppressor activity from tobacco plants The EMBO Journal. ,vol. 3, pp. 351- 356 ,(1984) , 10.1002/J.1460-2075.1984.TB01810.X
Andrew E. Firth, Norma M. Wills, Raymond F. Gesteland, John F. Atkins, Stimulation of stop codon readthrough: frequent presence of an extended 3′ RNA structural element Nucleic Acids Research. ,vol. 39, pp. 6679- 6691 ,(2011) , 10.1093/NAR/GKR224