Neuron-specific ELAV/Hu proteins suppress HuR mRNA during neuronal differentiation by alternative polyadenylation
| العنوان: | Neuron-specific ELAV/Hu proteins suppress HuR mRNA during neuronal differentiation by alternative polyadenylation |
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| المؤلفون: | Jack D. Keene, Kyle D. Mansfield |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Gene isoform, Polyadenylation, Neurogenesis, RNA Stability, Biology, Cell Line, 03 medical and health sciences, 0302 clinical medicine, MRNA polyadenylation, Genetics, Protein biosynthesis, RNA Isoforms, Humans, 3' Untranslated Regions, 030304 developmental biology, AU-rich element, Regulation of gene expression, Neurons, 0303 health sciences, Three prime untranslated region, Translation (biology), Molecular biology, ELAV Proteins, Gene Expression Regulation, Protein Biosynthesis, RNA, 030217 neurology & neurosurgery |
| الوصف: | The ubiquitously expressed RNA-binding protein HuR increases the stability and translation of mRNAs encoding growth regulatory proteins that promote proliferation in a variety of cell types. However, the three neuron-specific ELAV/Hu proteins, HuB, HuC and HuD, while binding to the same types of mRNAs, are required instead for neuronal differentiation, and it becomes difficult to reconcile these contrary functions when all four Hu proteins are expressed in the same neuron. HuR mRNA exists as three alternatively polyadenylated variants, a 1.5-kb testes-specific mRNA isoform, a ubiquitous 2.4-kb isoform and a 6.0-kb isoform that we now show is induced during neuronal differentiation and appears to be neuron-specific. This 6.0-kb neuron-specific mRNA isoform is inherently less stable and produces less HuR protein than the ubiquitous 2.4-kb mRNA. Furthermore, we show that neuronal HuB, HuC and HuD, as well as HuR itself, can bind at the 2.4-kb mRNA polyadenylation site, and when overexpressed can affect alternative polyadenylation to generate an extended HuR 3′-UTR that is translationally suppressed. We propose that the regulation of HuR protein expression by alternative polyadenylation allows neurons to post-transcriptionally regulate mRNAs-encoding factors required for proliferation versus differentiation to facilitate neuronal differentiation. |
| اللغة: | English |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6ef6b7d69af7c8f4f9d20906a8367a64 http://europepmc.org/articles/PMC3315332 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6ef6b7d69af7c8f4f9d20906a8367a64 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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