Involvement of Hu and heterogeneous nuclear ribonucleoprotein K in neuronal differentiation through p21 mRNA post-transcriptional regulation

Masato Yano, Hirotaka J. Okano, Hideyuki Okano

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

The Hu family is a group of neuronal RNA-binding proteins required for neuronal differentiation in the developing nervous system. Previously, Hu proteins have been shown to enhance the stabilization and/or translation of target mRNAs, such as p21 (CIP1), by binding to AU-rich elements in untranslated regions (UTRs). In this study, we show that Hu induces p21 expression, cell cycle arrest, and neuronal differentiation in mouse neuroblastoma N1E-115 cells. p21 expression is also up-regulated during Me2SO-induced differentiation in N1E-115 cells and is controlled by post-transcriptional mechanisms through its 3′-UTR. To investigate the molecular mechanisms of Hu functions, we used a proteomics strategy to isolate Hu-interacting proteins and identified heterogeneous nuclear ribonucleoprotein (hnRNP) K. hnRNP K also specifically binds to CU-rich sequences in p21 mRNA 3′-UTR and represses its translation in both nonneuronal and neuronal cells. Further, using RNA interference experiments, we show that the Hu-p21 pathway contributes to the regulation of neurite outgrowth and proliferation in N1E-115 cells, and this pathway is antagonized by hnRNP K. Our results suggest a model in which the mutually antagonistic action of two RNA-binding proteins, Hu and hnRNP K, control the timing of the switch from proliferation to neuronal differentiation through the post-transcriptional regulation of p21 mRNA.

Original languageEnglish
Pages (from-to)12690-12699
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number13
DOIs
Publication statusPublished - 2005 Apr 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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