Prion protein and neuronal differentiation: quantitative analysis of prnp gene expression in a murine inducible neuroectodermal progenitor

Pathogenic prion protein (PrPSc), converted from normal prion protein (PrPC), causes prion disease. Although prion disease has been reported in several mammalian species, chickens are known to show strong resistance to prion diseases. In addition to chickens, the domestic duck occupies a large proportion in the poultry industry and may be regarded as a potential resistant host against prion disease. However, the DNA sequence of the prion protein gene (PRNP) has not been reported in domestic ducks. Here, we performed amplicon sequencing targeting the duck PRNP gene with the genomic DNA of Pekin ducks. In addition, we aligned the PrP sequence of the Pekin duck with that of various species using ClustalW2 and carried out phylogenetic analysis using Molecular Evolutionary Genetics Analysis X (MEGA X). We also constructed the structural modeling of the tertiary and secondary structures in avian PrP using SWISS-MODEL. Last, we investigated the aggregation propensity on Pekin duck PrP using AMYCO. We first reported the DNA sequence of the PRNP gene in Pekin ducks and found that the PrP sequence of Pekin ducks is more similar to that of geese than to that of chickens and mallards (wild ducks). Interestingly, Pekin duck PrP showed a high proportion of β-sheets compared to that of chicken PrP, and a high aggregation propensity compared to that of avian PrPs. However, Pekin duck PrP with substitutions of chicken-specific amino acids showed reduced aggregation propensities. To the best of our knowledge, this is the first report on the genetic characteristics of the PRNP sequence in Pekin ducks.

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REST is a key regulator in brain-specific homeobox gene expression during neuronal differentiation

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2007.04947.x ◽

2007 ◽

Vol 0 (0) ◽

pp. 071018045431010-??? ◽

Cited By ~ 4

Author(s):

So Yun Park ◽

Jae Bum Kim ◽

Yong-Mahn Han

Keyword(s):

Gene Expression ◽

Neuronal Differentiation ◽

Homeobox Gene

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The First Meta-Analysis of the M129V Single-Nucleotide Polymorphism (SNP) of the Prion Protein Gene (PRNP) with Sporadic Creutzfeldt–Jakob Disease

Cells ◽

10.3390/cells10113132 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3132

Author(s):

Yong-Chan Kim ◽

Byung-Hoon Jeong

Keyword(s):

Prion Protein ◽

Protein Gene ◽

Meta Analysis ◽

Prnp Gene ◽

Case Control ◽

Prion Protein Gene ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Jakob Disease ◽

Sporadic Cjd

Prion diseases are fatal, chronic, and incurable neurodegenerative diseases caused by pathogenic forms of prion protein (PrPSc) derived from endogenous forms of prion protein (PrPC). Several case–control and genome-wide association studies have reported that the M129V polymorphism of the human prion protein gene (PRNP) is significantly associated with susceptibility to sporadic Creutzfeldt–Jakob disease (CJD). However, since some case–control studies have not shown these associations, the results remain controversial. We collected data that contain the genotype and allele frequencies of the M129V single-nucleotide polymorphism (SNP) of the PRNP gene and information on ethnic backgrounds from sporadic CJD patients. We performed a meta-analysis by collecting data from eligible studies to evaluate the association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD. We found a very strong association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD using a meta-analysis for the first time. We validated the eligibility of existing reports and found severe heterogeneity in some previous studies. We also found that the MM homozygote is a potent risk factor for sporadic CJD compared to the MV heterozygote in the heterozygote comparison model (MM vs. MV, odds ratio = 4.9611, 95% confidence interval: 3.4785; 7.0758, p < 1 × 10−10). To the best of our knowledge, this was the first meta-analysis assessment of the relationship between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD.

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Single cell 3’UTR analysis identifies changes in alternative polyadenylation throughout neuronal differentiation and in autism

10.1101/2020.08.12.247627 ◽

2020 ◽

Author(s):

Manuel Göpferich ◽

Nikhil Oommen George ◽

Ana Domingo Muelas ◽

Alex Bizyn ◽

Rosa Pascual ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Neural Stem Cells ◽

Single Cell ◽

Neuronal Differentiation ◽

Mrna Translation ◽

Autism Spectrum ◽

Adult Brain ◽

Control Of Gene Expression ◽

Risk Genes

SUMMARYAutism spectrum disorder (ASD) is a neurodevelopmental disease affecting social behavior. Many of the high-confident ASD risk genes relate to mRNA translation. Specifically, many of these genes are involved in regulation of gene expression for subcellular compartmentalization of proteins1. Cis-regulatory motifs that often localize to 3’- and 5’-untranslated regions (UTRs) offer an additional path for posttranscriptional control of gene expression. Alternative cleavage and polyadenylation (APA) affect 3’UTR length thereby influencing the presence or absence of regulatory elements. However, APA has not yet been addressed in the context of neurodevelopmental disorders. Here we used single cell 3’end sequencing to examine changes in 3’UTRs along the differentiation from neural stem cells (NSCs) to neuroblasts within the adult brain. We identified many APA events in genes involved in neurodevelopment, many of them being high confidence ASD risk genes. Further, analysis of 3’UTR lengths in single cells from ASD and healthy individuals detected longer 3’UTRs in ASD patients. Motif analysis of modulated 3’UTRs in the mouse adult neurogenic lineage and ASD-patients revealed enrichment of the cytoplasmic and polyadenylation element (CPE). This motif is bound by CPE binding protein 4 (CPEB4). In human and mouse data sets we observed co-regulation of CPEB4 and the CPEB-binding synaptic adhesion molecule amyloid beta precursor-like protein 1 (APLP1). We show that mice deficient in APLP1 show aberrant regulation of APA, decreased number of neural stem cells, and autistic-like traits. Our findings indicate that APA is used for control of gene expression along neuronal differentiation and is altered in ASD patients.

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Trans-activation of the human SOX3 promoter by MAZ in NT2/D1 cells

Archives of Biological Sciences ◽

10.2298/abs0803379k ◽

2008 ◽

Vol 60 (3) ◽

pp. 379-387 ◽

Cited By ~ 2

Author(s):

Natasa Kovacevic-Grujicic ◽

Kazunari Yokoyama ◽

Milena Stevanovic

Keyword(s):

Gene Expression ◽

Neuronal Differentiation ◽

Gene Transcription ◽

Binding Sites ◽

Promoter Activity ◽

Zinc Finger Protein ◽

Mobility Shift ◽

Finger Protein ◽

Sox3 Gene

In this study, we examine the role of three highly conserved putative binding sites for Myc-associated zinc finger protein (MAZ) in regulation of the human SOX3 gene expression. Electrophoretic mobility shift and supershift assays indicate that complexes formed at two out of three MAZ sites of the human SOX3 promoter involve ubiquitously expressed MAZ protein. Furthermore, in cotransfection experiments we demonstrate that MAZ acts as a positive regulator of SOX3 gene transcription in both undifferentiated and RA-differentiated NT2/D1 cells. Although MAZ increased both basal and RA-induced promoter activity, our results suggest that MAZ does not contribute to RA inducibility of the SOX3 promoter during neuronal differentiation of NT2/D1 cells.

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