Selenocysteine biosynthesis and incorporation may require supramolecular complexes

Abstract

Selenoproteins are a protein family in which the amino acid, selenocysteine (Sec) is incorporated cotranslationally at UGA stop codons. Selenoprotein synthesis requires unique RNA and protein factors in order to recode UGA. In eukaryotes, both the biosynthesis and incorporation of Sec employ nucleo-cytoplasmic shuttling of multiple protein factors, and this shuttling appears to play crucial roles in the functions of these factors. A dynamic series of supramolecular complexes may increase the efficiency of Sec incorporation, as well as the recycling of the Sec biosynthesis factors. This chapter will review the putative functions of these factors and explore the protein-nucleic acid and protein-protein interactions that define their biological roles. In addition, preliminary attempts to isolate supramolecular translation complexes from in vivo and in vitro systems will be discussed. Recent evidence suggests that both the biosynthesis of Sec-tRNA and the incorporation of Sec are physically coupled within supramolecular complexes that retain and coordinate the many factors required, tRNA channeling systems for the standard 20 amino acids rely on cotranslational complexes for spatial and temporal regulation of the multiple enzymatic factors responsible for aminoacyl-tRNA recycling. This chapter draws parallels between these functionally equivalent systems in eukaryotes.