Facile Recoding of Selenocysteine in Nature

Abstract

Selenocysteine (Sec or U) is encoded by UGA, a stop codon reassigned by a Sec-specific elongation factor and a distinctive RNA structure. To discover possible code variations in extant organisms we analyzed 6.4 trillion base pairs of metagenomic sequences and 24,903 microbial genomes for tRNASec species. As expected, UGA is the predominant Sec codon in use. We also found tRNASec species that recognize the stop codons UAG and UAA, and ten sense codons. Selenoprotein synthesis programmed by UAG in Geodermatophilus and Blastococcus, and by the Cys codon UGU in Aeromonas salmonicida was confirmed by metabolic labeling with 75Se or mass spectrometry. Other tRNASec species with different anticodons enabled Escherichia coli to synthesize active formate dehydrogenase H, a selenoenzyme. This illustrates the ease by which the genetic code may evolve new coding schemes, possibly aiding organisms to adapt to changing environments. Our results reveal that the genetic code is much more flexible than previously thought.

Selenocysteine Insertion at a Predefined UAG Codon in a Release Factor 1 (RF1)-depleted Escherichia coli Host Strain Bypasses Species Barriers in Recombinant Selenoprotein Translation

“…6B). Additional codon-anticodon variations have been reported, but have not yet been analyzed at depth regarding yields and efficiencies in final products of recombinant selenoproteins (29,49). Importantly, here we found that if UAG-directed TrxR1 production is performed in the RF1-depleted C321.⌬A host strain with a maintained variant SECIS element, almost full Sec content is achieved due to the fact that termination no longer occurs (Fig.…”

Rewriting the Genetic Code

“…Given the vast amount of new genomic and metagenomic DNA sequence information generated in the past few years, we document here the current knowledge of natural deviations from the standard genetic code (45, 61, 79, 92, 94, 98, 115, 125, 134, 157) (Figure 2) (Supplemental Figure 1). Previously, it was well known that Candida yeast reassigns the CUG codon from leucine (Leu) to serine (Ser) (60) and that many ciliates reassign either the UGA stop codon or both the UAA and the UAG stop codons to a canonical amino acid (12, 61, 88, 119) (Figure 2).…”

Human selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elements

“…Selenocysteine, Sec, specification illustrates both aspects. It is specified by UGU in Aeromonas salmonicida , UAG in Blastococcus and UGA in Escherichia coli and eukaryotes [1]. In the great majority of vertebrate mRNAs, UGA specifies termination and how its meaning is dynamically redefined to specify selenocysteine in a very small number of coding sequences, 25 in humans, is of great interest.…”