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The selenoprotein P 3’ untranslated region is an RNA binding protein platform that fine tunes selenocysteine incorporation

Selenoproteins contain the 21st amino acid, selenocysteine (Sec), which is incorporated at select UGA codons when a specialized hairpin sequence, the Sec insertion sequence (SECIS) element, is present in the 3’ UTR. Aside from the SECIS, selenoprotein mRNA 3’ UTRs are not conserved between different...

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Autores principales: Shetty, Sumangala P., Kiledjian, Nora T., Copeland, Paul R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337670/
https://www.ncbi.nlm.nih.gov/pubmed/35905095
http://dx.doi.org/10.1371/journal.pone.0271453
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author Shetty, Sumangala P.
Kiledjian, Nora T.
Copeland, Paul R.
author_facet Shetty, Sumangala P.
Kiledjian, Nora T.
Copeland, Paul R.
author_sort Shetty, Sumangala P.
collection PubMed
description Selenoproteins contain the 21st amino acid, selenocysteine (Sec), which is incorporated at select UGA codons when a specialized hairpin sequence, the Sec insertion sequence (SECIS) element, is present in the 3’ UTR. Aside from the SECIS, selenoprotein mRNA 3’ UTRs are not conserved between different selenoproteins within a species. In contrast, the 3’-UTR of a given selenoprotein is often conserved across species, which supports the hypothesis that cis-acting elements in the 3’-UTR other than the SECIS exert post-transcriptional control on selenoprotein expression. In order to determine the function of one such SECIS context, we chose to focus on the plasma selenoprotein, SELENOP, which is required to maintain selenium homeostasis as a selenium transport protein that contains 10 Sec residues. It is unique in that its mRNA contains two SECIS elements in the context of a highly conserved 843-nucleotide 3’ UTR. Here we have used RNA affinity chromatography and identified PTBP1 as the major RNA binding protein that specifically interacts with the sequence between the two SECIS elements. We then used CRISPR/Cas9 genome editing to delete two regions surrounding the first SECIS element. We found that these sequences are involved in regulating SELENOP mRNA and protein levels, which are inversely altered as a function of selenium concentrations.
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spelling pubmed-93376702022-07-30 The selenoprotein P 3’ untranslated region is an RNA binding protein platform that fine tunes selenocysteine incorporation Shetty, Sumangala P. Kiledjian, Nora T. Copeland, Paul R. PLoS One Research Article Selenoproteins contain the 21st amino acid, selenocysteine (Sec), which is incorporated at select UGA codons when a specialized hairpin sequence, the Sec insertion sequence (SECIS) element, is present in the 3’ UTR. Aside from the SECIS, selenoprotein mRNA 3’ UTRs are not conserved between different selenoproteins within a species. In contrast, the 3’-UTR of a given selenoprotein is often conserved across species, which supports the hypothesis that cis-acting elements in the 3’-UTR other than the SECIS exert post-transcriptional control on selenoprotein expression. In order to determine the function of one such SECIS context, we chose to focus on the plasma selenoprotein, SELENOP, which is required to maintain selenium homeostasis as a selenium transport protein that contains 10 Sec residues. It is unique in that its mRNA contains two SECIS elements in the context of a highly conserved 843-nucleotide 3’ UTR. Here we have used RNA affinity chromatography and identified PTBP1 as the major RNA binding protein that specifically interacts with the sequence between the two SECIS elements. We then used CRISPR/Cas9 genome editing to delete two regions surrounding the first SECIS element. We found that these sequences are involved in regulating SELENOP mRNA and protein levels, which are inversely altered as a function of selenium concentrations. Public Library of Science 2022-07-29 /pmc/articles/PMC9337670/ /pubmed/35905095 http://dx.doi.org/10.1371/journal.pone.0271453 Text en © 2022 Shetty et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Shetty, Sumangala P.
Kiledjian, Nora T.
Copeland, Paul R.
The selenoprotein P 3’ untranslated region is an RNA binding protein platform that fine tunes selenocysteine incorporation
title The selenoprotein P 3’ untranslated region is an RNA binding protein platform that fine tunes selenocysteine incorporation
title_full The selenoprotein P 3’ untranslated region is an RNA binding protein platform that fine tunes selenocysteine incorporation
title_fullStr The selenoprotein P 3’ untranslated region is an RNA binding protein platform that fine tunes selenocysteine incorporation
title_full_unstemmed The selenoprotein P 3’ untranslated region is an RNA binding protein platform that fine tunes selenocysteine incorporation
title_short The selenoprotein P 3’ untranslated region is an RNA binding protein platform that fine tunes selenocysteine incorporation
title_sort selenoprotein p 3’ untranslated region is an rna binding protein platform that fine tunes selenocysteine incorporation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337670/
https://www.ncbi.nlm.nih.gov/pubmed/35905095
http://dx.doi.org/10.1371/journal.pone.0271453
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