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Publication : The polyadenosine RNA-binding protein ZC3H14 interacts with the THO complex and coordinately regulates the processing of neuronal transcripts.

First Author  Morris KJ Year  2018
Journal  Nucleic Acids Res Volume  46
Issue  13 Pages  6561-6575
PubMed ID  29912477 Mgi Jnum  J:265757
Mgi Id  MGI:6193231 Doi  10.1093/nar/gky446
Citation  Morris KJ, et al. (2018) The polyadenosine RNA-binding protein ZC3H14 interacts with the THO complex and coordinately regulates the processing of neuronal transcripts. Nucleic Acids Res 46(13):6561-6575
abstractText  The polyadenosine RNA-binding protein ZC3H14 is important in RNA processing. Although ZC3H14 is ubiquitously expressed, mutation of the ZC3H14 gene causes a non-syndromic form of intellectual disability. Here, we examine the function of ZC3H14 in the brain by identifying ZC3H14-interacting proteins using unbiased mass spectrometry. Through this analysis, we identified physical interactions between ZC3H14 and multiple RNA processing factors. Notably, proteins that comprise the THO complex were amongst the most enriched proteins. We demonstrate that ZC3H14 physically interacts with THO components and that these proteins are required for proper RNA processing, as loss of ZC3H14 or THO components leads to extended bulk poly(A) tail length. Furthermore, we identified the transcripts Atp5g1 and Psd95 as shared RNA targets of ZC3H14 and the THO complex. Our data suggest that ZC3H14 and the THO complex are important for proper processing of Atp5g1 and Psd95 RNA, as depletion of ZC3H14 or THO components leads to decreased steady-state levels of each mature transcript accompanied by accumulation of Atp5g1 and Psd95 pre-mRNA in the cytoplasm. Taken together, this work provides the first unbiased identification of nuclear ZC3H14-interacting proteins from the brain and links the functions of ZC3H14 and the THO complex in the processing of RNA.
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