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      Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention

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      Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention..pdf (2.077Mb)
      Author
      Yap, Karen.
      Lim, Zhao Qin.
      Khandelia, Piyush.
      Friedman, Brad.
      Makeyev, Eugene V.
      Date of Issue
      2012
      School
      School of Biological Sciences
      Version
      Published version
      Abstract
      Differentiated cells acquire unique structural and functional traits through coordinated expression of lineage-specific genes. An extensive battery of genes encoding components of the synaptic transmission machinery and specialized cytoskeletal proteins is activated during neurogenesis, but the underlying regulation is not well understood. Here we show that genes encoding critical presynaptic proteins are transcribed at a detectable level in both neurons and nonneuronal cells. However, in nonneuronal cells, the splicing of 3′-terminal introns within these genes is repressed by the polypyrimidine tract-binding protein (Ptbp1). This inhibits the export of incompletely spliced mRNAs to the cytoplasm and triggers their nuclear degradation. Clearance of these intron-containing transcripts occurs independently of the nonsense-mediated decay (NMD) pathway but requires components of the nuclear RNA surveillance machinery, including the nuclear pore-associated protein Tpr and the exosome complex. When Ptbp1 expression decreases during neuronal differentiation, the regulated introns are spliced out, thus allowing the accumulation of translation-competent mRNAs in the cytoplasm. We propose that this mechanism counters ectopic and precocious expression of functionally linked neuron-specific genes and ensures their coherent activation in the appropriate developmental context.
      Subject
      DRNTU::Science::Biological sciences
      Type
      Journal Article
      Series/Journal Title
      Genes & development
      Rights
      © 2012 Cold Spring Harbor Laboratory Press. This paper was published in Genes & Development and is made available as an electronic reprint (preprint) with permission of Cold Spring Harbor Laboratory Press. The paper can be found at the following official DOI: [http://dx.doi.org/10.1101/gad.188037.112]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
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      http://dx.doi.org/10.1101/gad.188037.112
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