The RNA-binding protein, ZC3H14, is required for proper poly(A) tail length control, expression of synaptic proteins, and brain function in mice Article Swipe
Jennifer Rha
,
Stephanie K. Jones
,
Jonathan A. Fidler
,
Ayan Banerjee
,
Sara W. Leung
,
Kevin J. Morris
,
Jennifer C. Wong
,
George Andrew S. Inglis
,
Lindsey Shapiro
,
Qiudong Deng
,
Alicia A. Cutler
,
Adam M. Hanif
,
Machelle T. Pardue
,
Ashleigh E. Schaffer
,
Nicholas T. Seyfried
,
Kenneth H. Moberg
,
Gary J. Bassell
,
Andrew Escayg
,
Paul S. García
,
Anita H. Corbett
·
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1093/hmg/ddx248
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1093/hmg/ddx248
A number of mutations in genes that encode ubiquitously expressed RNA-binding proteins cause tissue specific disease. Many of these diseases are neurological in nature revealing critical roles for this class of proteins in the brain. We recently identified mutations in a gene that encodes a ubiquitously expressed polyadenosine RNA-binding protein, ZC3H14 (Zinc finger CysCysCysHis domain-containing protein 14), that cause a nonsyndromic, autosomal recessive form of intellectual disability. This finding reveals the molecular basis for disease and provides evidence that ZC3H14 is essential for proper brain function. To investigate the role of ZC3H14 in the mammalian brain, we generated a mouse in which the first common exon of the ZC3H14 gene, exon 13 is removed (Zc3h14Δex13/Δex13) leading to a truncated ZC3H14 protein. We report here that, as in the patients, Zc3h14 is not essential in mice. Utilizing these Zc3h14Δex13/Δex13mice, we provide the first in vivo functional characterization of ZC3H14 as a regulator of RNA poly(A) tail length. The Zc3h14Δex13/Δex13 mice show enlarged lateral ventricles in the brain as well as impaired working memory. Proteomic analysis comparing the hippocampi of Zc3h14+/+ and Zc3h14Δex13/Δex13 mice reveals dysregulation of several pathways that are important for proper brain function and thus sheds light onto which pathways are most affected by the loss of ZC3H14. Among the proteins increased in the hippocampi of Zc3h14Δex13/Δex13 mice compared to control are key synaptic proteins including CaMK2a. This newly generated mouse serves as a tool to study the function of ZC3H14 in vivo.
Related Topics
Concepts
Biology
Zinc finger
Exon
RNA-binding protein
Gene
Genetics
Cell biology
Loss function
RNA
Phenotype
Transcription factor
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/hmg/ddx248
- https://academic.oup.com/hmg/article-pdf/26/19/3663/24339678/ddx248.pdf
- OA Status
- bronze
- Cited By
- 41
- References
- 105
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2725302594
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2725302594Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/hmg/ddx248Digital Object Identifier
- Title
-
The RNA-binding protein, ZC3H14, is required for proper poly(A) tail length control, expression of synaptic proteins, and brain function in miceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2017Year of publication
- Publication date
-
2017-06-28Full publication date if available
- Authors
-
Jennifer Rha, Stephanie K. Jones, Jonathan A. Fidler, Ayan Banerjee, Sara W. Leung, Kevin J. Morris, Jennifer C. Wong, George Andrew S. Inglis, Lindsey Shapiro, Qiudong Deng, Alicia A. Cutler, Adam M. Hanif, Machelle T. Pardue, Ashleigh E. Schaffer, Nicholas T. Seyfried, Kenneth H. Moberg, Gary J. Bassell, Andrew Escayg, Paul S. García, Anita H. CorbettList of authors in order
- Landing page
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https://doi.org/10.1093/hmg/ddx248Publisher landing page
- PDF URL
-
https://academic.oup.com/hmg/article-pdf/26/19/3663/24339678/ddx248.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
-
https://academic.oup.com/hmg/article-pdf/26/19/3663/24339678/ddx248.pdfDirect OA link when available
- Concepts
-
Biology, Zinc finger, Exon, RNA-binding protein, Gene, Genetics, Cell biology, Loss function, RNA, Phenotype, Transcription factorTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
41Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 4, 2024: 7, 2023: 3, 2022: 4, 2021: 5Per-year citation counts (last 5 years)
- References (count)
-
105Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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