Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells.
In mice, Quaking (Qk) is required for myelin formation; in humans, it has been associated with psychiatric disease. QK regulates the stability, subcellular localization, and alternative splicing of several myelin-related transcripts, yet little is known about how QK governs these activities. Here, w...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC3017110?pdf=render |
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author | N Ruth Zearfoss Carina C Clingman Brian M Farley Lisa M McCoig Sean P Ryder |
author_facet | N Ruth Zearfoss Carina C Clingman Brian M Farley Lisa M McCoig Sean P Ryder |
author_sort | N Ruth Zearfoss |
collection | DOAJ |
description | In mice, Quaking (Qk) is required for myelin formation; in humans, it has been associated with psychiatric disease. QK regulates the stability, subcellular localization, and alternative splicing of several myelin-related transcripts, yet little is known about how QK governs these activities. Here, we show that QK enhances Hnrnpa1 mRNA stability by binding a conserved 3' UTR sequence with high affinity and specificity. A single nucleotide mutation in the binding site eliminates QK-dependent regulation, as does reduction of QK by RNAi. Analysis of exon expression across the transcriptome reveals that QK and hnRNP A1 regulate an overlapping subset of transcripts. Thus, a simple interpretation is that QK regulates a large set of oligodendrocyte precursor genes indirectly by increasing the intracellular concentration of hnRNP A1. Together, the data show that hnRNP A1 is an important QK target that contributes to its control of myelin gene expression. |
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institution | Directory Open Access Journal |
issn | 1553-7390 1553-7404 |
language | English |
last_indexed | 2024-12-16T06:42:30Z |
publishDate | 2011-01-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS Genetics |
spelling | doaj.art-7f253cc95e474de9b72af70c5d6752ea2022-12-21T22:40:38ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-01-0171e100126910.1371/journal.pgen.1001269Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells.N Ruth ZearfossCarina C ClingmanBrian M FarleyLisa M McCoigSean P RyderIn mice, Quaking (Qk) is required for myelin formation; in humans, it has been associated with psychiatric disease. QK regulates the stability, subcellular localization, and alternative splicing of several myelin-related transcripts, yet little is known about how QK governs these activities. Here, we show that QK enhances Hnrnpa1 mRNA stability by binding a conserved 3' UTR sequence with high affinity and specificity. A single nucleotide mutation in the binding site eliminates QK-dependent regulation, as does reduction of QK by RNAi. Analysis of exon expression across the transcriptome reveals that QK and hnRNP A1 regulate an overlapping subset of transcripts. Thus, a simple interpretation is that QK regulates a large set of oligodendrocyte precursor genes indirectly by increasing the intracellular concentration of hnRNP A1. Together, the data show that hnRNP A1 is an important QK target that contributes to its control of myelin gene expression.http://europepmc.org/articles/PMC3017110?pdf=render |
spellingShingle | N Ruth Zearfoss Carina C Clingman Brian M Farley Lisa M McCoig Sean P Ryder Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells. PLoS Genetics |
title | Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells. |
title_full | Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells. |
title_fullStr | Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells. |
title_full_unstemmed | Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells. |
title_short | Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells. |
title_sort | quaking regulates hnrnpa1 expression through its 3 utr in oligodendrocyte precursor cells |
url | http://europepmc.org/articles/PMC3017110?pdf=render |
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