Prominent expression of the selenoprotein thioredoxin reductase in the medullary rays of the rat kidney and thioredoxin reductase mRNA variants differing at the 5' untranslated region.
The mammalian selenoprotein thioredoxin reductase is a central enzyme in protection against oxidative damage or the redox control of cell function. Previously a neuroblastoma-cell-derived 2193 bp cDNA for rat thioredoxin reductase 1 (TrxR1) was characterized [Zhong, Arnér, Ljung, Aslund and Holmgren (1998) J. Biol. Chem. 273, 8581-8591]. Here, the major rat TrxR1 mRNA was determined as 3.5 kb by Northern blotting. A corresponding full-length 3360 bp liver-derived cDNA was cloned and sequenced, being extended in the 3' untranslated region (3' UTR) compared with the previous clone. Among tissues examined, lowest TrxR1 mRNA levels were found in spleen and testis and highest in liver and kidney. High expression in kidney was unexpected and in situ hybridization of adult rat kidney was performed. This revealed a highly structured expression pattern with the mRNA being prominently synthesized in the proximal tubules of the medullary rays. Analysing rat kidney cDNA, a 5' UTR domain of TrxR1 was found that was different from that in liver- or neuroblastoma-derived cDNA clones. The kidney-derived 5' UTR mRNA domain was instead highly similar to kidney-derived cDNA variants of murine apolipoprotein E. By sequence determination of the rat genomic sequence upstream of the open reading frame for TrxR1, an exon was encountered that encoded a third alternative 5' UTR domain that could also be expressed, as confirmed by its presence in a mouse skin TrxR1 cDNA clone. It can therefore be concluded that TrxR1 mRNA is expressed in at least three different variants that differ at their 5' UTRs.
Rundlöf
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AK
Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska institutet, S-171 77 Stockholm, Sweden.
Carlsten
M
M
Giacobini
M M
MM
Arnér
E S
ES
D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000032:analysis / Q000235:genetics*; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000201:enzymology; D009928:Organ Specificity; D011506:Proteins / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051140:Selenoproteins; D016415:Sequence Alignment; D012867:Skin / Q000201:enzymology; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics*
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D011506:Proteins; D051140:Selenoproteins; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase; C516125:Txnrd1 protein, mouse; C516126:Txnrd1 protein, rat