Translational Redefinition of UGA Codons Is Regulated by Selenium Availability

Howard, Michael; Carlson, Bradley A.; Anderson, Christine B.; Hatfield, Dolph L.

doi:10.1074/jbc.m113.481051

Cited by 91 publications

(83 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1B) with a mean footprint size surrounding 32 nucleotides (Fig. 1C), consistent with previous results obtained in mammalian cells or tissues (18)(19)(20)(21) as well as with ribosome size. Biological reproducibility for both RNA-Seq and Ribo-Seq was high ( Fig.…”

Section: Resultssupporting

confidence: 91%

See 1 more Smart Citation

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

Atger

Gobet

Marquis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

208

284

View full text Add to dashboard Cite

Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5′-Terminal Oligo Pyrimidine tract (5′-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5′-UTR (TISU) motif. The increased translation efficiency of 5′-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.circadian rhythms | ribosome profiling | mRNA translation | 5′-TOP sequences | TISU motifs L iving organisms on Earth are subjected to light-dark cycles caused by rotation of the Earth around the sun. To anticipate these changes, virtually all organisms have acquired a circadian timing system during evolution that allows a better adaptation to their environment. As a consequence, most aspects of their physiology are orchestrated in a rhythmic way by the circadian clock (from the Latin circa diem, meaning "about a day"), an endogenous and autonomous oscillator with a period of around 24 h (1, 2). Not surprisingly, perturbations of this clock in mammals lead to pathologies including psychiatric, metabolic, and vascular disorders (1,3,4). At the organismal scale, the oscillatory clockwork is organized in a hierarchal manner. Within the suprachiasmatic nuclei (SCN) of the hypothalamus, the "master clock" receives light input via the retina and communicates timing signals to "enslave" oscillators in peripheral organs (1, 2). The molecular oscillator consists of interconnected transcriptional and translational feedback loops, in which multiple layers of control, including temporal posttranscriptional and posttranslational regulation, play important roles (5). These additional layers of regulation are largely coordinated by systemic cues originating from circadian clock and/or feeding-coordinated rhythmic metabolism, allowing the adjustment of the molecular clo...

show abstract

Section: Resultssupporting

confidence: 91%

“…Owing to the large number of samples, we developed a simplified and faster protocol for ribosome profiling library generation, similar to that in ref. 18. Briefly, ribosome footprints (RFPs) ends were modified with polynucleotide kinase to generate libraries using 5′-and 3′-mRNA adapters.…”

Section: Resultsmentioning

confidence: 99%

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

Atger

Gobet

Marquis

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

208

284

View full text Add to dashboard Cite

show abstract

“…The idea that the decreased decoding efficiency of the UGASec codon in stress-related selenoproteins may affect the susceptibility of selenoprotein transcripts to NMD under Se-deficient conditions has been further supported by recent ribosome profiling studies (145). At the translational level, Se deficiency results in decreased ribosome density downstream of the Sec-encoding UGA codon of several selenoprotein mRNAs, suggesting a slower rate of Sec incorporation (145).…”

Section: E Regulation Of Selenoprotein Expressionmentioning

confidence: 99%

Selenoproteins: Molecular Pathways and Physiological Roles

Labunskyy

Hatfield

Gladyshev³

2014

Physiological Reviews

Self Cite

986

792

View full text Add to dashboard Cite

Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by selenium-containing proteins (selenoproteins) that are present in all three domains of life. Although selenoproteins represent diverse molecular pathways and biological functions, all these proteins contain at least one selenocysteine (Sec), a seleniumcontaining amino acid, and most serve oxidoreductase functions. Sec is cotranslationally inserted into nascent polypeptide chains in response to the UGA codon, whose normal function is to terminate translation. To decode UGA as Sec, organisms evolved the Sec insertion machinery that allows incorporation of this amino acid at specific UGA codons in a process requiring a cis-acting Sec insertion sequence (SECIS) element. Although the basic mechanisms of Sec synthesis and insertion into proteins in both prokaryotes and eukaryotes have been studied in great detail, the identity and functions of many selenoproteins remain largely unknown. In the last decade, there has been significant progress in characterizing selenoproteins and selenoproteomes and understanding their physiological functions. We discuss current knowledge about how these unique proteins perform their functions at the molecular level and highlight new insights into the roles that selenoproteins play in human health.

show abstract

“…(B) Initiating ribosomes profile and elongating ribosomes profile for the second exon of the mouse Stard10 gene. The description is the same as for panel A except that the initiating ribosomes profile was generated from two studies 15, 18 and the elongating ribosomes profile from five studies 15, 16, 37, 39, 40. (C) Elongating ribosomes profile for the first exon of the human SCAMP3 gene.…”

mentioning

confidence: 99%

“…The description is the same as for panel A except that the ribosome profiles were generated from the same studies as in Fig. 1B and the mRNA‐seq coverage plot was generated using data from four studies 16, 37, 39, 40.…”

mentioning

confidence: 99%

GWIPS‐viz as a tool for exploring ribosome profiling evidence supporting the synthesis of alternative proteoforms

et al. 2015

View full text Add to dashboard Cite

The boundaries of protein coding sequences are more difficult to define at the 5′ end than at the 3′ end due to potential multiple translation initiation sites (TISs). Even in the presence of phylogenetic data, the use of sequence information only may not be sufficient for the accurate identification of TISs. Traditional proteomics approaches may also fail because the N‐termini of newly synthesized proteins are often processed. Thus ribosome profiling (ribo‐seq), producing a snapshot of the ribosome distribution across the entire transcriptome, is an attractive experimental technique for the purpose of TIS location exploration. The GWIPS‐viz (Genome Wide Information on Protein Synthesis visualized) browser (http://gwips.ucc.ie) provides free access to the genomic alignments of ribo‐seq data and corresponding mRNA‐seq data along with relevant annotation tracks. In this brief, we illustrate how GWIPS‐viz can be used to explore the ribosome occupancy at the 5′ ends of protein coding genes to assess the activity of AUG and non‐AUG TISs responsible for the synthesis of proteoforms with alternative or heterogeneous N‐termini. The presence of ribo‐seq tracks for various organisms allows for cross‐species comparison of orthologous genes and the availability of datasets from multiple laboratories permits the assessment of the technical reproducibility of the ribosome densities.

show abstract

Translational Redefinition of UGA Codons Is Regulated by Selenium Availability

Cited by 91 publications

References 45 publications

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

Selenoproteins: Molecular Pathways and Physiological Roles

GWIPS‐viz as a tool for exploring ribosome profiling evidence supporting the synthesis of alternative proteoforms

Contact Info

Product

Resources

About