Tarpey, P. S., Raymond, F. L., Nguyen, L. S., Rodriguez, J., Hackett, A., Vandeleur, L., Smith, R., Shoubridge, C., Edkins, S., Stevens, C., O'Meara, S., Tofts, C., Barthorpe, S., Buck, G., Cole, J., Halliday, K., Hills, K., Jones, D., Mironenko, T., Perry, J., Varian, J., West, S., Widaa, S., Teague, J., Dicks, E., Butler, A., Menzies, A., Richardson, D., Jenkinson, A., Shepherd, R., Raine, K., Moon, J., Luo, Y., Parnau, J., Bhat, S. S., Gardner, A., Corbett, M., Brooks, D., Thomas, P., Parkinson-Lawrence, E., Porteous, M. E., Warner, J. P., Sanderson, T., Pearson, P., Simensen, R. J., Skinner, C., Hoganson, G., Superneau, D., Wooster, R., Bobrow, M., Turner, G., Stevenson, R. E., Schwartz, C. E., Futreal, P. A., Srivastava, A. K., Stratton, M. R., Gecz, J. (2007) Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. NATURE GENETICS, 39 (9). pp. 1127-1133. ISSN 1061-4036

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Abstract

Nonsense- mediated mRNA decay ( NMD) is of universal biological significance(1-3). It has emerged as an important global RNA, DNA and translation regulatory pathway(4). By systematically sequencing 737 genes ( annotated in the Vertebrate Genome Annotation database) on the human X chromosome in 250 families with X- linked mental retardation, we identified mutations in the UPF3 regulator of nonsense transcripts homolog B ( yeast) ( UPF3B) leading to protein truncations in three families: two with the Lujan- Fryns phenotype5,6 and one with the FG phenotype7. We also identified a missense mutation in another family with nonsyndromic mental retardation. Three mutations lead to the introduction of a premature termination codon and subsequent NMD of mutant UPF3B mRNA. Protein blot analysis using lymphoblastoid cell lines from affected individuals showed an absence of the UPF3B protein in two families. The UPF3B protein is an important component of the NMD surveillance machinery(8,9). Our results directly implicate abnormalities of NMD in human disease and suggest at least partial redundancy of NMD pathways.

Item Type:	Article
Authors (ICR Faculty only):	Stratton, Mike
All Authors:	Tarpey, P. S., Raymond, F. L., Nguyen, L. S., Rodriguez, J., Hackett, A., Vandeleur, L., Smith, R., Shoubridge, C., Edkins, S., Stevens, C., O'Meara, S., Tofts, C., Barthorpe, S., Buck, G., Cole, J., Halliday, K., Hills, K., Jones, D., Mironenko, T., Perry, J., Varian, J., West, S., Widaa, S., Teague, J., Dicks, E., Butler, A., Menzies, A., Richardson, D., Jenkinson, A., Shepherd, R., Raine, K., Moon, J., Luo, Y., Parnau, J., Bhat, S. S., Gardner, A., Corbett, M., Brooks, D., Thomas, P., Parkinson-Lawrence, E., Porteous, M. E., Warner, J. P., Sanderson, T., Pearson, P., Simensen, R. J., Skinner, C., Hoganson, G., Superneau, D., Wooster, R., Bobrow, M., Turner, G., Stevenson, R. E., Schwartz, C. E., Futreal, P. A., Srivastava, A. K., Stratton, M. R., Gecz, J.
Uncontrolled Keywords:	EXON-JUNCTION COMPLEX; MARFANOID HABITUS; FG SYNDROME; SURVEILLANCE; TRANSLATION; ELEGANS; HUPF3B; GENE; FORM
Research teams:	ICR divisions > Breast Cancer Research > Genetic Susceptibility ICR divisions > Genetics and Epidemiology > Genetic Susceptibility
Depositing User:	Users 6 not found.
Date Deposited:	10 Jan 2008 12:14
Last Modified:	20 Apr 2010 10:34
URI:	http://publications.icr.ac.uk/id/eprint/5327

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