A synthetic tRNA for EF‐Tu mediated selenocysteine incorporation in vivo and in vitro

Abstract

Incorporation of selenocysteine (Sec) in bacteria requires a UGA codon that is reassigned to Sec by the Sec‐specific elongation factor SelB and a conserved mRNA motif (SECIS element). These requirements severely restrict the engineering of selenoproteins. Earlier, a synthetic tRNASec was reported that allowed canonical Sec incorporation by EF‐Tu; however, serine misincorporation limited its scope. We report a superior tRNASec variant (tRNAUTuX) that facilitates EF‐Tu dependent stoichiometric Sec insertion in response to UAG both in vivo in Escherichia coli and in vitro in a cellfree protein synthesis system. We also demonstrate recoding of several sense codons in a SelB supplemented cell‐free system. These advances in Sec incorporation will aid rational design and directed evolution of selenoproteins.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jul 06, 2015
Source ID
10.1016/j.febslet.2015.06.039

Entities

People

  • Alexander Feiock
  • Corwin Miller
  • Dieter Söll
  • Kevan Ip
  • Laure Prat
  • Markus J. Bröcker
  • Miklós Veszprémi
  • Napon Chirathivat

Organizations

  • Defense Advanced Research Projects Agency
  • National Institute of General Medical Sciences

Tags

Fields of Study

  • Biology

Readers

  • Military Engineering.
  • Molecular Genetics
  • Rocket Propulsion.