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Trans-effectors of nonsense-mediated...

Laken, Haley A.

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Trans-effectors of nonsense-mediated RNA decay.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Trans-effectors of nonsense-mediated RNA decay./
作者:	Laken, Haley A.
面頁冊數:	119 p.
附註:	Source: Dissertation Abstracts International, Volume: 60-04, Section: B, page: 1441.
Contained By:	Dissertation Abstracts International60-04B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9927100
ISBN:	0599268670

Trans-effectors of nonsense-mediated RNA decay.
Laken, Haley A.

Trans-effectors of nonsense-mediated RNA decay. - 119 p.

Source: Dissertation Abstracts International, Volume: 60-04, Section: B, page: 1441.

Thesis (Ph.D.)--The Johns Hopkins University, 1999.

All eukaryotes that have been studied to date possess the ability to detect and degrade transcripts that contain a premature signal for the termination of translation. Nonsense-mediated RNA decay (NMD) likely protects the organism from deleterious peptides that could be expressed from nonsense alleles if the corresponding transcripts were stabilized. A deeper understanding of the mechanism of NMD may provide insight into the molecular mechanism of disease. Studies of the NMD pathway in mammalian cells have been greatly facilitated by the use of available information from the budding yeast S. cerevisiae .

ISBN: 0599268670Subjects--Topical Terms:

1017719
Biology, Molecular.

Trans-effectors of nonsense-mediated RNA decay.
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502 $a Thesis (Ph.D.)--The Johns Hopkins University, 1999.
520 $a All eukaryotes that have been studied to date possess the ability to detect and degrade transcripts that contain a premature signal for the termination of translation. Nonsense-mediated RNA decay (NMD) likely protects the organism from deleterious peptides that could be expressed from nonsense alleles if the corresponding transcripts were stabilized. A deeper understanding of the mechanism of NMD may provide insight into the molecular mechanism of disease. Studies of the NMD pathway in mammalian cells have been greatly facilitated by the use of available information from the budding yeast S. cerevisiae .
520 $a Based on the similarities in the NMD pathway between yeast and humans, we sought to determine whether the two pathways utilize functionally related proteins. Using the sequence for yeast UPF1, a human cDNA encoding a protein with strong homology to Upf1p, termed rent1 ( regulator of nonsense transcripts) was isolated. The two proteins show 58% residue identity and 80% conservation. Rent1 is the first identified mammalian protein that contains all of the putative functional elements found in Upf1p including zinc finger-like nucleotide binding domains and all of the motifs common to members of helicase superfamily I. Expression of a chimeric protein, containing the central region of rentl flanked by the extreme N- and C-termini of Upf1p, complemented the Upf1-deficient growth phenotype in yeast. Additionally, expression of a dominant negative allele of rentl in mammalian cells stabilized nonsense transcripts 2--3 fold. Analysis of rent1 in mammalian cells revealed that it is expressed in all tissues tested and is localized primarily in the cytoplasm.
520 $a Compelling evidence exists for either or both a nuclear and cytoplasmic localization of nonsense-mediated RNA decay. A unifying model would suggest that coding potential can be interpreted independent of conventional cytoplasmic translation. To test this hypothesis we used S. cerevisiae strains encoding conditional mutant forms of Ded1p, a protein essential for translation initiation, we observed full efficiency of nonsense decay despite 98% inhibition of translation. These data support a model in which NMD is mediated by unconventional mechanisms that interpret transcript coding potential.
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