Processive Recoding and Metazoan Evolution of Selenoprotein P: Up to 132 UGAs in Molluscs. Issue 22 (8th November 2019)

• Record Type: Journal Article
• Authors: Baclaocos, Janinah; Santesmasses, Didac; Mariotti, Marco; Bierła, Katarzyna; Vetick, Michael B.; Lynch, Sharon; McAllen, Rob; Mackrill, John J.; Loughran, Gary; Guigó, Roderic; Szpunar, Joanna; Copeland, Paul R.; Gladyshev, Vadim N.; Atkins, John F.
• Is Part Of: Journal of molecular biology. Volume 431:Issue 22(2019)
• Page Start: 4381
• Page End: 4407
• Publication Date: 2019-11-08
• Subjects: selenoprotein -- selenocysteine -- recoding -- dynamic redefinition -- evolution; Sec selenocysteine -- SECIS selenocysteine insertion sequence -- SRE Sec redefinition element -- SelenoP selenoprotein P -- ISL initiation stem loop -- Cys cysteine -- CDS coding sequence -- RRL rabbit reticulocyte lysate -- ORF open reading frame -- RPF ribosome-protected fragment -- NMD nonsense-mediated decay -- ICP-MS inductively coupled mass spectrometry -- URE UGA-redefinition efficiency -- GST Glutathione Sepharose Transferase; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2019.08.007
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Selenoproteins typically contain a single selenocysteine, the 21st amino acid, encoded by a context-redefined UGA. However, human selenoprotein P (SelenoP) has a redox-functioning selenocysteine in its N-terminal domain and nine selenium transporter-functioning selenocysteines in its C-terminal domain. Here we show that diverse SelenoP genes are present across metazoa with highly variable numbers of Sec-UGAs, ranging from a single UGA in certain insects, to 9 in common spider, and up to 132 in bivalve molluscs. SelenoP genes were shaped by a dynamic evolutionary process linked to selenium usage. Gene evolution featured modular expansions of an ancestral multi-Sec domain, which led to particularly Sec-rich SelenoP proteins in many aquatic organisms. We focused on molluscs, and chose Pacific oyster Magallana gigas as experimental model. We show that oyster SelenoP mRNA with 46 UGAs is translated full-length in vivo . Ribosome profiling indicates that selenocysteine specification occurs with ∼ 5% efficiency at UGA1 and approaches 100% efficiency at distal 3′ UGAs. We report genetic elements relevant to its expression, including a leader open reading frame and an RNA structure overlapping the initiation codon that modulates ribosome progression in a selenium-dependent manner. Unlike their mammalian counterparts, the two SECIS elements in oyster SelenoP (3′UTR recoding elements) do not show functional differentiation in vitro . Oysters can increase their tissue selenium level up to 50-fold upon supplementation, which also results in extensive changes in selenoprotein expression. Graphical Abstract: Unlabelled Image Highlights: SelenoP has 10 selenocysteine-UGAs in human, but what about other metazoa?. Remarkable diversity of SelenoP: from 1 Sec-UGA in insects to 132 in bivalves. Translation and in vivo Sec-incorporation of a 46-UGA SelenoP in Pacific oyster. Regulatory RNA elements in oyster SelenoP with roles in initiation and Sec-decoding. New insights into SelenoP evolution and processive translation of multiple Sec-UGAs.