The splicing activator DAZAP1 integrates splicing control into MEK/Erk-regulated cell proliferation and migration

Rajarshi Choudhury, Sreerupa Ghose Roy, Yihsuan S. Tsai, Ashutosh Tripathy, Lee M. Graves and Zefeng Wang ()
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Rajarshi Choudhury: University of North Carolina
Sreerupa Ghose Roy: University of North Carolina
Yihsuan S. Tsai: University of North Carolina
Ashutosh Tripathy: University of North Carolina
Lee M. Graves: University of North Carolina
Zefeng Wang: University of North Carolina

Nature Communications, 2014, vol. 5, issue 1, 1-16

Abstract: Abstract Alternative splicing of pre-messenger RNA (mRNA) is a critical stage of gene regulation in response to environmental stimuli. Here we show that DAZAP1, an RNA-binding protein involved in mammalian development and spermatogenesis, promotes inclusion of weak exons through specific recognition of diverse cis-elements. The carboxy-terminal proline-rich domain of DAZAP1 interacts with and neutralizes general splicing inhibitors, and is sufficient to activate splicing when recruited to pre-mRNA. This domain is phosphorylated by the MEK/Erk (extracellular signal-regulated protein kinase) pathway and this modification is essential for the splicing regulatory activity and the nuclear/cytoplasmic translocation of DAZAP1. Using mRNA-seq, we identify endogenous splicing events regulated by DAZAP1, many of which are involved in maintaining cell growth. Knockdown or over-expression of DAZAP1 causes a cell proliferation defect. Taken together, these studies reveal a molecular mechanism that integrates splicing control into MEK/Erk-regulated cell proliferation.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4078

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DOI: 10.1038/ncomms4078

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