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A regulatory role for Sec tRNA[Ser]Sec in selenoprotein synthesis.
RNA. 2004 Jul; 10(7):1142-52.RNA

Abstract

Selenium is biologically active through the functions of selenoproteins that contain the amino acid selenocysteine. This amino acid is translated in response to in-frame UGA codons in mRNAs that include a SECIS element in its 3' untranslated region, and this process requires a unique tRNA, referred to as tRNA([Ser]Sec). The translation of UGA as selenocysteine, rather than its use as a termination signal, is a candidate restriction point for the regulation of selenoprotein synthesis by selenium. A specialized reporter construct was used that permits the evaluation of SECIS-directed UGA translation to examine mechanisms of the regulation of selenoprotein translation. Using SECIS elements from five different selenoprotein mRNAs, UGA translation was quantified in response to selenium supplementation and alterations in tRNA([Ser]Sec) levels and isoform distributions. Although each of the evaluated SECIS elements exhibited differences in their baseline activities, each was stimulated to a similar extent by increased selenium or tRNA([Ser]Sec) levels and was inhibited by diminished levels of the methylated isoform of tRNA([Ser]Sec) achieved using a dominant-negative acting mutant tRNA([Ser]Sec). tRNA([Ser]Sec) was found to be limiting for UGA translation under conditions of high selenoprotein mRNA in both a transient reporter assay and in cells with elevated GPx-1 mRNA. This and data indicating increased amounts of the methylated isoform of tRNA([Ser]Sec) during selenoprotein translation indicate that it is this isoform that is translationally active and that selenium-induced tRNA methylation is a mechanism of regulation of the synthesis of selenoproteins.

Authors+Show Affiliations

Department of Human Nutrition, University of Illinois at Chicago, 1919 West Taylor Street, MC517, Chicago, IL 60612, USA.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15208449

Citation

Jameson, Ruth R., and Alan M. Diamond. "A Regulatory Role for Sec tRNA[Ser]Sec in Selenoprotein Synthesis." RNA (New York, N.Y.), vol. 10, no. 7, 2004, pp. 1142-52.
Jameson RR, Diamond AM. A regulatory role for Sec tRNA[Ser]Sec in selenoprotein synthesis. RNA. 2004;10(7):1142-52.
Jameson, R. R., & Diamond, A. M. (2004). A regulatory role for Sec tRNA[Ser]Sec in selenoprotein synthesis. RNA (New York, N.Y.), 10(7), 1142-52.
Jameson RR, Diamond AM. A Regulatory Role for Sec tRNA[Ser]Sec in Selenoprotein Synthesis. RNA. 2004;10(7):1142-52. PubMed PMID: 15208449.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A regulatory role for Sec tRNA[Ser]Sec in selenoprotein synthesis. AU - Jameson,Ruth R, AU - Diamond,Alan M, PY - 2004/6/23/pubmed PY - 2004/8/24/medline PY - 2004/6/23/entrez SP - 1142 EP - 52 JF - RNA (New York, N.Y.) JO - RNA VL - 10 IS - 7 N2 - Selenium is biologically active through the functions of selenoproteins that contain the amino acid selenocysteine. This amino acid is translated in response to in-frame UGA codons in mRNAs that include a SECIS element in its 3' untranslated region, and this process requires a unique tRNA, referred to as tRNA([Ser]Sec). The translation of UGA as selenocysteine, rather than its use as a termination signal, is a candidate restriction point for the regulation of selenoprotein synthesis by selenium. A specialized reporter construct was used that permits the evaluation of SECIS-directed UGA translation to examine mechanisms of the regulation of selenoprotein translation. Using SECIS elements from five different selenoprotein mRNAs, UGA translation was quantified in response to selenium supplementation and alterations in tRNA([Ser]Sec) levels and isoform distributions. Although each of the evaluated SECIS elements exhibited differences in their baseline activities, each was stimulated to a similar extent by increased selenium or tRNA([Ser]Sec) levels and was inhibited by diminished levels of the methylated isoform of tRNA([Ser]Sec) achieved using a dominant-negative acting mutant tRNA([Ser]Sec). tRNA([Ser]Sec) was found to be limiting for UGA translation under conditions of high selenoprotein mRNA in both a transient reporter assay and in cells with elevated GPx-1 mRNA. This and data indicating increased amounts of the methylated isoform of tRNA([Ser]Sec) during selenoprotein translation indicate that it is this isoform that is translationally active and that selenium-induced tRNA methylation is a mechanism of regulation of the synthesis of selenoproteins. SN - 1355-8382 UR - https://www.unboundmedicine.com/medline/citation/15208449/A_regulatory_role_for_Sec_tRNA[Ser]Sec_in_selenoprotein_synthesis_ L2 - http://www.rnajournal.org/cgi/pmidlookup?view=long&pmid=15208449 DB - PRIME DP - Unbound Medicine ER -