Linked Life Data

15611090

Source:http://linkedlifedata.com/resource/pubmed/id/15611090

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-2-14
pubmed:abstractText
Selenocysteine (Sec) is the 21st amino acid in the genetic code. Its tRNA is variably methylated on the 2'-O-hydroxyl site of the ribosyl moiety at position 34 (Um34). Herein, we identified a role of Um34 in regulating the expression of some, but not all, selenoproteins. A strain of knock-out transgenic mice was generated, wherein the Sec tRNA gene was replaced with either wild type or mutant Sec tRNA transgenes. The mutant transgene yielded a tRNA that lacked two base modifications, N(6)-isopentenyladenosine at position 37 (i(6)A37) and Um34. Several selenoproteins, including glutathione peroxidases 1 and 3, SelR, and SelT, were not detected in mice rescued with the mutant transgene, whereas other selenoproteins, including thioredoxin reductases 1 and 3 and glutathione peroxidase 4, were expressed in normal or reduced levels. Northern blot analysis suggested that other selenoproteins (e.g. SelW) were also poorly expressed. This novel regulation of protein expression occurred at the level of translation and manifested a tissue-specific pattern. The available data suggest that the Um34 modification has greater influence than the i(6)A37 modification in regulating the expression of various mammalian selenoproteins and Um34 is required for synthesis of several members of this protein class. Many proteins that were poorly rescued appear to be involved in responses to stress, and their expression is also highly dependent on selenium in the diet. Furthermore, their mRNA levels are regulated by selenium and are subject to nonsense-mediated decay. Overall, this study described a novel mechanism of regulation of protein expression by tRNA modification that is in turn regulated by levels of the trace element, selenium.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5542-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15611090-Animals, pubmed-meshheading:15611090-Blotting, Northern, pubmed-meshheading:15611090-Blotting, Western, pubmed-meshheading:15611090-Female, pubmed-meshheading:15611090-Fertility, pubmed-meshheading:15611090-Gene Expression Regulation, pubmed-meshheading:15611090-Glutathione Peroxidase, pubmed-meshheading:15611090-Litter Size, pubmed-meshheading:15611090-Male, pubmed-meshheading:15611090-Methionine Sulfoxide Reductases, pubmed-meshheading:15611090-Methylation, pubmed-meshheading:15611090-Mice, pubmed-meshheading:15611090-Proteins, pubmed-meshheading:15611090-RNA, Messenger, pubmed-meshheading:15611090-RNA, Transfer, Amino Acyl, pubmed-meshheading:15611090-Selenium, pubmed-meshheading:15611090-Selenoprotein W, pubmed-meshheading:15611090-Selenoproteins, pubmed-meshheading:15611090-Spermatozoa
pubmed:year
2005
pubmed:articleTitle
Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA.
pubmed:affiliation
Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.