Translation regulation of mammalian selenoproteins

• Published in: Biochimica et biophysica acta. General subjects Vol. 1862; no. 11; pp. 2480 - 2492
• Main Authors: Vindry, Caroline, Ohlmann, Théophile, Chavatte, Laurent
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2018; Elsevier
• Subjects: 3' untranslated regions; antioxidant activity; Bacteriology; cardiovascular diseases; catalytic activity; cysteine; genetic code; homeostasis; human diseases; Immunology; infectious diseases; Life Sciences; mammals; Microbiology and Parasitology; molecular biology; neoplasms; nutrient deficiencies; risk; Sec-tRNA[Ser]Sec; SECIS; selenium; Selenocysteine; Selenoprotein; selenoproteins; stop codon; sulfur; translation (genetics); Translational control; UGA recoding; Virology; Selenocysteine; SECIS; Selenoprotein; Sec-tRNA[Ser]Sec; UGA recoding; Translational control; Sec-tRNA([Ser]Sec)
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2018.05.010

Interest in selenium research has considerably grown over the last decades owing to the association of selenium deficiencies with an increased risk of several human diseases, including cancers, cardiovascular disorders and infectious diseases. The discovery of a genetically encoded 21st amino acid, selenocysteine, is a fascinating breakthrough in molecular biology as it is the first addition to the genetic code deciphered in the 1960s. Selenocysteine is a structural and functional analog of cysteine, where selenium replaces sulfur, and its presence is critical for the catalytic activity of selenoproteins. The insertion of selenocysteine is a non-canonical translational event, based on the recoding of a UGA codon in selenoprotein mRNAs, normally used as a stop codon in other cellular mRNAs. Two RNA molecules and associated partners are crucial components of the selenocysteine insertion machinery, the Sec-tRNA[Ser]Sec devoted to UGA codon recognition and the SECIS elements located in the 3′UTR of selenoprotein mRNAs. The translational UGA recoding event is a limiting stage of selenoprotein expression and its efficiency is regulated by several factors. The control of selenoproteome expression is crucial for redox homeostasis and antioxidant defense of mammalian organisms. In this review, we summarize current knowledge on the co-translational insertion of selenocysteine into selenoproteins, and its layers of regulation. [Display omitted] •Insertion of selenocysteine in selenoproteins is a non-canonical translational event, based on the recoding of a UGA codon, normally a stop codon•The Sec-tRNA[Ser]Sec, the SECIS element and associated partners are central components for selenocysteine insertion•The translational UGA recoding is a limiting stage that controls selenoprotein expression in response to various stimuli