Regulation of alpha-synuclein expression in alcohol-preferring and -non preferring rats

Tiebing Liang, Lucinda G. Carr

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The α-synuclein (Snca) gene is expressed at higher levels in alcohol-naïve, inbred alcohol-preferring (iP) rats than in alcohol-non preferring (iNP) rats. Snca modulates dopamine transmission and the dopamineregic system, which play a role in mediating the rewarding properties of alcohol consumption. Thus, understanding regulation of Snca gene expression could provide insight into the relationship of Snca and alcohol consumption. To study regulation of rat Snca expression, 1912 bp of the iP and iNP 5′-regions were cloned and sequenced. 5′-rapid amplification of cDNA ends (RACE), primer extension and RT-PCR mapped three transcription start site clusters (clusters TSS1, TSS2 and TSS3), suggesting that the Snca proximal promoter region has a complex architecture. This proximal promoter region has three TATA-less core promoters containing SP1 binding sites, initiator elements and downstream core promoter elements, which are often located in such promoters. Snca-luc constructs transiently transfected into SK-N-SH neuroblastoma cells showed that the region from -1912 to -1746 contained a strong core promoter, and that the entire approximately 2 kb region had significant promoter activity. Five polymorphisms identified between the iP and iNP in the proximal promoter region did not influence differential expression between the strains. In contrast, a single nucleotide polymorphism (SNP) at +679 in the 3′-untranslated region (UTR) resulted in a 1.3-fold longer half-life of iP mRNA compared with iNP mRNA, which is consistent with the differential expression observed between the iP and iNP strains. These results suggest that regulation of rat Snca gene expression is complex and may contribute to alcohol preference in the iP rats.

Original languageEnglish
Pages (from-to)470-482
Number of pages13
JournalJournal of Neurochemistry
Volume99
Issue number2
DOIs
StatePublished - Oct 2006

Fingerprint

alpha-Synuclein
Rats
Alcohols
Genetic Promoter Regions
Alcohol Drinking
Polymorphism
Gene expression
Synucleins
Messenger RNA
Transcription Initiation Site
Gene Expression Regulation
3' Untranslated Regions
Neuroblastoma
Single Nucleotide Polymorphism
Half-Life
Dopamine

Keywords

  • Alpha-synuclein
  • Expression
  • Gene regulation
  • mRNA stability
  • Polymorphism
  • Rat selected strains

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Regulation of alpha-synuclein expression in alcohol-preferring and -non preferring rats. / Liang, Tiebing; Carr, Lucinda G.

In: Journal of Neurochemistry, Vol. 99, No. 2, 10.2006, p. 470-482.

Research output: Contribution to journalArticle

@article{7a5a911fa20042809549c2cb0be3bb29,
title = "Regulation of alpha-synuclein expression in alcohol-preferring and -non preferring rats",
abstract = "The α-synuclein (Snca) gene is expressed at higher levels in alcohol-na{\"i}ve, inbred alcohol-preferring (iP) rats than in alcohol-non preferring (iNP) rats. Snca modulates dopamine transmission and the dopamineregic system, which play a role in mediating the rewarding properties of alcohol consumption. Thus, understanding regulation of Snca gene expression could provide insight into the relationship of Snca and alcohol consumption. To study regulation of rat Snca expression, 1912 bp of the iP and iNP 5′-regions were cloned and sequenced. 5′-rapid amplification of cDNA ends (RACE), primer extension and RT-PCR mapped three transcription start site clusters (clusters TSS1, TSS2 and TSS3), suggesting that the Snca proximal promoter region has a complex architecture. This proximal promoter region has three TATA-less core promoters containing SP1 binding sites, initiator elements and downstream core promoter elements, which are often located in such promoters. Snca-luc constructs transiently transfected into SK-N-SH neuroblastoma cells showed that the region from -1912 to -1746 contained a strong core promoter, and that the entire approximately 2 kb region had significant promoter activity. Five polymorphisms identified between the iP and iNP in the proximal promoter region did not influence differential expression between the strains. In contrast, a single nucleotide polymorphism (SNP) at +679 in the 3′-untranslated region (UTR) resulted in a 1.3-fold longer half-life of iP mRNA compared with iNP mRNA, which is consistent with the differential expression observed between the iP and iNP strains. These results suggest that regulation of rat Snca gene expression is complex and may contribute to alcohol preference in the iP rats.",
keywords = "Alpha-synuclein, Expression, Gene regulation, mRNA stability, Polymorphism, Rat selected strains",
author = "Tiebing Liang and Carr, {Lucinda G.}",
year = "2006",
month = "10",
doi = "10.1111/j.1471-4159.2006.04111.x",
language = "English",
volume = "99",
pages = "470--482",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Regulation of alpha-synuclein expression in alcohol-preferring and -non preferring rats

AU - Liang, Tiebing

AU - Carr, Lucinda G.

PY - 2006/10

Y1 - 2006/10

N2 - The α-synuclein (Snca) gene is expressed at higher levels in alcohol-naïve, inbred alcohol-preferring (iP) rats than in alcohol-non preferring (iNP) rats. Snca modulates dopamine transmission and the dopamineregic system, which play a role in mediating the rewarding properties of alcohol consumption. Thus, understanding regulation of Snca gene expression could provide insight into the relationship of Snca and alcohol consumption. To study regulation of rat Snca expression, 1912 bp of the iP and iNP 5′-regions were cloned and sequenced. 5′-rapid amplification of cDNA ends (RACE), primer extension and RT-PCR mapped three transcription start site clusters (clusters TSS1, TSS2 and TSS3), suggesting that the Snca proximal promoter region has a complex architecture. This proximal promoter region has three TATA-less core promoters containing SP1 binding sites, initiator elements and downstream core promoter elements, which are often located in such promoters. Snca-luc constructs transiently transfected into SK-N-SH neuroblastoma cells showed that the region from -1912 to -1746 contained a strong core promoter, and that the entire approximately 2 kb region had significant promoter activity. Five polymorphisms identified between the iP and iNP in the proximal promoter region did not influence differential expression between the strains. In contrast, a single nucleotide polymorphism (SNP) at +679 in the 3′-untranslated region (UTR) resulted in a 1.3-fold longer half-life of iP mRNA compared with iNP mRNA, which is consistent with the differential expression observed between the iP and iNP strains. These results suggest that regulation of rat Snca gene expression is complex and may contribute to alcohol preference in the iP rats.

AB - The α-synuclein (Snca) gene is expressed at higher levels in alcohol-naïve, inbred alcohol-preferring (iP) rats than in alcohol-non preferring (iNP) rats. Snca modulates dopamine transmission and the dopamineregic system, which play a role in mediating the rewarding properties of alcohol consumption. Thus, understanding regulation of Snca gene expression could provide insight into the relationship of Snca and alcohol consumption. To study regulation of rat Snca expression, 1912 bp of the iP and iNP 5′-regions were cloned and sequenced. 5′-rapid amplification of cDNA ends (RACE), primer extension and RT-PCR mapped three transcription start site clusters (clusters TSS1, TSS2 and TSS3), suggesting that the Snca proximal promoter region has a complex architecture. This proximal promoter region has three TATA-less core promoters containing SP1 binding sites, initiator elements and downstream core promoter elements, which are often located in such promoters. Snca-luc constructs transiently transfected into SK-N-SH neuroblastoma cells showed that the region from -1912 to -1746 contained a strong core promoter, and that the entire approximately 2 kb region had significant promoter activity. Five polymorphisms identified between the iP and iNP in the proximal promoter region did not influence differential expression between the strains. In contrast, a single nucleotide polymorphism (SNP) at +679 in the 3′-untranslated region (UTR) resulted in a 1.3-fold longer half-life of iP mRNA compared with iNP mRNA, which is consistent with the differential expression observed between the iP and iNP strains. These results suggest that regulation of rat Snca gene expression is complex and may contribute to alcohol preference in the iP rats.

KW - Alpha-synuclein

KW - Expression

KW - Gene regulation

KW - mRNA stability

KW - Polymorphism

KW - Rat selected strains

UR - http://www.scopus.com/inward/record.url?scp=33749165901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749165901&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2006.04111.x

DO - 10.1111/j.1471-4159.2006.04111.x

M3 - Article

VL - 99

SP - 470

EP - 482

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -