Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells
Biochemistry & Molecular Pharmacology
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
*3' Untranslated Regions; Alternative Splicing; Animals; Base Sequence; Cell Differentiation; Cell Line; Conserved Sequence; Exons; *Gene Expression Regulation; Heterogeneous-Nuclear Ribonucleoprotein Group A-B; Humans; Mice; Myelin-Associated Glycoprotein; Oligodendroglia; Oligonucleotide Array Sequence Analysis; RNA Stability; RNA, Small Interfering; RNA-Binding Proteins; Rats; Sequence Alignment
Biochemistry | Genetics and Genomics | Molecular Genetics
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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Citation: PLoS Genet. 2011 Jan 6;7(1):e1001269. doi: 10.1371/journal.pgen.1001269. Link to article on publisher's site
Zearfoss, Nancy R.; Clingman, Carina C.; Farley, Brian M.; McCoig, Lisa M.; and Ryder, Sean P., "Quaking regulates Hnrnpa1 expression through its 3' UTR in oligodendrocyte precursor cells" (2011). GSBS Student Publications. 1820.