High impact information on Trsp

• Staf is a zinc finger protein that we recently identified as the transcriptional activator of the RNA polymerase III-transcribed selenocysteine tRNA gene [1].
• The mouse tRNASec gene (Trsp) maps to a proximal segment of chromosome 7 [2].
• Selenoprotein biosynthesis is mediated by tRNASec, which inserts selenocysteine at UGA codons in a complex, context-specific manner [2].
• Although the level of tRNASec was reduced to about 50%-80% of the wild type in most organs, one of the selenoproteins, glutathione peroxidase, remained unaffected in the levels of its mRNA, protein, and enzyme activity, indicating that the haploid amount of tRNASec is not limiting in its biosynthesis [2].
• This study investigates the consequence of disrupting an upstream enhancer region of the mouse tRNA(Sec) gene (Trsp) known as the distal sequence element (DSE) by use of a conditional repair gene targeting strategy, in which a 3.2-kb insertion was introduced into the promoter of the gene [3].

Biological context of Trsp

• The mouse gene encoding tRNA([Ser]Sec) (Trsp) was isolated from a genomic library and sequenced [4].
• Further analysis of targeted heterozygous adult mice revealed that the enhancer activity of the DSE is tissue dependent since, in contrast to liver, heart does not require the DSE for normal expression of Trsp [3].
• The distal sequence element of the selenocysteine tRNA gene is a tissue-dependent enhancer essential for mouse embryogenesis [3].
• The predicted amino acid sequence of m-Staf is highly homologous to that of Staf, another selenocysteine tRNA gene transcription activating factor of Xenopus laevis [5].
• Opal suppressor phosphoserine tRNA gene and pseudogene are located on human chromosomes 19 and 22, respectively [6].

Anatomical context of Trsp

• Selective removal of the selenocysteine tRNA [Ser]Sec gene (Trsp) in mouse mammary epithelium [7].
• We have isolated and characterized a cDNA encoding a transcription activating factor for the mouse selenocysteine tRNA (tRNAsec) gene from mouse mammary gland [5].

Associations of Trsp with chemical compounds

• Selective inhibition of selenocysteine tRNA maturation and selenoprotein synthesis in transgenic mice expressing isopentenyladenosine-deficient selenocysteine tRNA [8].
• Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA [9].
• The mechanism of selenocysteine synthesis on tRNASec in mammals was previously studied by means of HSe- as a Se donor to synthesize selenocysteine [10].

Other interactions of Trsp

• Using restriction fragment length variants (RFLVs) in interspecific backcross mice between Mus musculus (C3H strain) and Mus spretus, the Trsp gene was mapped to the proximal region of mouse Chr 7, cosegregating with octamer-binding transcription factor-2 (Otf2) [4].
• Thus, the conditional Trsp knockout mouse allows tissue-specific manipulation of Sec tRNA and selenoprotein expression, suggesting that this approach will provide a useful tool for studying the role of selenoproteins in health [7].
• In addition, we examined the effects of selenium levels in the diet and perturbations in selenocysteine tRNA function on TGR biosynthesis and found that expression of this protein was regulated by both selenium and tRNA status in liver, but was more resistant to this regulation in testes [11].

References