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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Main Authors: N Ruth Zearfoss, Carina C Clingman, Brian M Farley, Lisa M McCoig, Sean P Ryder
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
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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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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