4.6 Article

Identification of a novel isoform of DHRS4 protein with a nuclear localization signal

Journal

GENE
Volume 494, Issue 2, Pages 161-167

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2011.12.033

Keywords

Alternative splicing; Nuclear localization signal; DHRS4 gene; NADP(H)-dependent retinol dehydrogenase/reductase

Funding

  1. National Natural Science Foundation of China [30970626, 31071153]
  2. National Basic Research Project of China, Program 973 [2010CD912503]

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The DHRS4 gene encodes an NADP(H)-dependent retinol dehydrogenase/reductase (NRDR) and plays an important role in regulating the synthesis of retinoic acid. In the present study, we identified a novel splice RNA variant, designated NRDRA2, of the human DHRS4 gene by RT-PCR, 3' RACE, and 5' RACE. NRDRA2 mRNA lacked exons 4 and 6, and had a shift in the reading frame when compared to DHRS4 mRNA, resulting in loss of the peroxisomal targeting signal of NRDR and gain of a nuclear localization signal in the predicted NRDRA2 protein. Endogenous NRDRA2 protein was identified in the human cervical carcinoma cell line HeLa by immunoprecipitation and mass spectrometric assay. A green fluorescent protein reporter assay showed that NRDRA2 protein mainly localized to the nuclei, confirming the sequence at its C-terminus as a legitimate nuclear localization signal sequence. This study identifies the alternative transcript variant NRDRA2 encoding a subcellular nuclear localized NRDRA2 protein. (C) 2011 Elsevier B.V. All rights reserved.

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