Splice variants of the human ZC3H14 gene generate multiple isoforms of a zinc finger polyadenosine RNA binding protein

Sara W Leung; Luciano H Apponi; Omar E Cornejo; Chad M Kitchen; Sandro R Valentini; Grace K Pavlath; Christine M Dunham; Anita H Corbett

doi:10.1016/j.gene.2009.02.022

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Splice variants of the human ZC3H14 gene generate multiple isoforms of a zinc finger polyadenosine RNA binding protein

Journal article

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Splice variants of the human ZC3H14 gene generate multiple isoforms of a zinc finger polyadenosine RNA binding protein

Sara W Leung, Luciano H Apponi, Omar E Cornejo, Chad M Kitchen, Sandro R Valentini, Grace K Pavlath, Christine M Dunham and Anita H Corbett

Gene, Vol.439(1), pp.71-78

2009

DOI: https://doi.org/10.1016/j.gene.2009.02.022

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https://hdl.handle.net/2376/114988

PMCID: PMC2680464

PMID: 19303045

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Abstract

Alternative splicing

Poly(A) binding proteins

S. cerevisiae Nab2

Nuclear speckle

mRNA processing/export

Post-transcriptional regulation of gene expression

The human ZC3H14 gene encodes an evolutionarily conserved Cys 3His zinc finger protein that binds specifically to polyadenosine RNA and is thus postulated to modulate post-transcriptional gene expression. Expressed sequence tag (EST) data predicts multiple splice variants of both human and mouse ZC3H14. Analysis of ZC3H14 expression in both human cell lines and mouse tissues confirms the presence of multiple alternatively spliced transcripts. Although all of these transcripts encode protein isoforms that contain the conserved C-terminal zinc finger domain, suggesting that they could all bind to polyadenosine RNA, they differ in other functionally important domains. Most of the alternative transcripts encode closely related proteins (termed isoforms 1, 2, 3, and 3short) that differ primarily in the inclusion of three small exons, 9, 10, and 11, resulting in predicted protein isoforms ranging from 82 to 64 kDa. Each of these closely related isoforms contains predicted classical nuclear localization signals (cNLS) within exons 7 and 11. Consistent with the presence of these putative nuclear targeting signals, these ZC3H14 isoforms are all localized to the nucleus. In contrast, an additional transcript encodes a smaller protein (34 kDa) with an alternative first exon (isoform 4). Consistent with the absence of the predicted cNLS motifs located in exons 7 and 11, ZC3H14 isoform 4 is localized to the cytoplasm. Both EST data and experimental data suggest that this variant is enriched in testes and brain. Using an antibody that detects endogenous ZC3H14 isoforms 1–3 reveals localization of these isoforms to nuclear speckles. These speckles co-localize with the splicing factor, SC35, suggesting a role for nuclear ZC3H14 in mRNA processing. Taken together, these results demonstrate that multiple transcripts encoding several ZC3H14 isoforms exist in vivo. Both nuclear and cytoplasmic ZC3H14 isoforms could have distinct effects on gene expression mediated by the common Cys 3His zinc finger polyadenosine RNA binding domain.

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Title: Splice variants of the human ZC3H14 gene generate multiple isoforms of a zinc finger polyadenosine RNA binding protein
Creators: Sara W Leung - Department of Biochemistry, Emory University School of Medicine, RRC Room 4117, 1510 Clifton Road, N.E., Atlanta, GA 30322-2430, USA
Luciano H Apponi - Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
Omar E Cornejo - Graduate Program in Population Biology, Ecology and Evolution, Emory University School of Medicine, Atlanta, GA 30322, USA
Chad M Kitchen - Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
Sandro R Valentini - Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University, UNESP, Araraquara, SP 14801-902, Brazil
Grace K Pavlath - Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
Christine M Dunham - Department of Biochemistry, Emory University School of Medicine, RRC Room 4117, 1510 Clifton Road, N.E., Atlanta, GA 30322-2430, USA
Anita H Corbett - Department of Biochemistry, Emory University School of Medicine, RRC Room 4117, 1510 Clifton Road, N.E., Atlanta, GA 30322-2430, USA
Publication Details: Gene, Vol.439(1), pp.71-78
Academic Unit: Biological Sciences, School of
Publisher: Elsevier B.V
Identifiers: 99900547867401842
Language: English
Resource Type: Journal article