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Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA.
J Biol Chem 2005; 280(7):5542-8JB

Abstract

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.

Authors+Show Affiliations

Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, MD 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15611090

Citation

Carlson, Bradley A., et al. "Selective Rescue of Selenoprotein Expression in Mice Lacking a Highly Specialized Methyl Group in Selenocysteine TRNA." The Journal of Biological Chemistry, vol. 280, no. 7, 2005, pp. 5542-8.
Carlson BA, Xu XM, Gladyshev VN, et al. Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA. J Biol Chem. 2005;280(7):5542-8.
Carlson, B. A., Xu, X. M., Gladyshev, V. N., & Hatfield, D. L. (2005). Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA. The Journal of Biological Chemistry, 280(7), pp. 5542-8.
Carlson BA, et al. Selective Rescue of Selenoprotein Expression in Mice Lacking a Highly Specialized Methyl Group in Selenocysteine TRNA. J Biol Chem. 2005 Feb 18;280(7):5542-8. PubMed PMID: 15611090.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA. AU - Carlson,Bradley A, AU - Xu,Xue-Ming, AU - Gladyshev,Vadim N, AU - Hatfield,Dolph L, Y1 - 2004/12/17/ PY - 2004/12/22/pubmed PY - 2005/4/19/medline PY - 2004/12/22/entrez SP - 5542 EP - 8 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 280 IS - 7 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15611090/Selective_rescue_of_selenoprotein_expression_in_mice_lacking_a_highly_specialized_methyl_group_in_selenocysteine_tRNA_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15611090 DB - PRIME DP - Unbound Medicine ER -