The utilization of selenocysteine-tRNA isoforms is regulated in part at the level of translation .

The tRNA for the 21st proteinogenic amino acid, selenocysteine, exists in mammalian cells as 2 isoforms differing by a single 2'-O-methylribosyl moiety at position 34 (Um34). These isoforms contain either 5-methoxycarbonylmethyluridine (mcmU) or 5-methoxycarbonylmethyl-2'-O-methyluridine (mcmUm) at position 34. The accumulation of the mcmUm isoform is tightly correlated with the expression of nonessential "stress response" selenoproteins such as glutathione peroxidase 1 (GPX1). The expression of essential selenoproteins, such as thioredoxin reductase 1 (TXNRD1), is not affected by changes in Sec-tRNA isoform accumulation. In this work we used purified mcmU and mcmUm Sec-tRNA isoforms to analyze possible differences in binding to the selenocysteine-specific elongation factor, EEFSEC, and the translation of and . Our results indicate that no major distinction between mcmU and mcmUm isoforms is made by the translation machinery, but a small consistent increase in translation is associated with the mcmUm isoform. These results implicate fundamental differences in translation efficiency in playing a role in regulating selenoprotein expression as a function of isoform accumulation.