Assessing serotonin receptor mRNA editing frequency by a novel ultra high-throughput sequencing method

被引：29

作者：

Abbas, Atheir I. ^{[6
]}

Urban, Daniel J.

Jensen, Niels H.

Farrell, Martilias S.

Kroeze, Wesley K.

Mieczkowski, Piotr ^{[2
]}

Wang, Zefeng

Roth, Bryan L. ^{[1
,3
,4
,5
]}

机构：

[1] Univ N Carolina, Dept Pharmacol, Natl Inst Mental Hlth, Psychoact Drug Screening Program,Sch Med, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[3] Univ N Carolina, Dept Psychiat, Sch Med, Chapel Hill, NC 27599 USA

[4] Univ N Carolina, Lineberger Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Dept Med Chem, Sch Pharm, Chapel Hill, NC 27599 USA

[6] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA

来源：

NUCLEIC ACIDS RESEARCH | 2010年 / 38卷 / 10期

基金：

美国国家卫生研究院;

关键词：

2C RECEPTOR; 5-HT2C RECEPTOR; REVERSIBLE TERMINATOR; HUMAN TRANSCRIPTOME; PREFRONTAL CORTEX; NERVOUS-SYSTEM; RAT-BRAIN; ADULT-RAT; GENE; BEHAVIOR;

D O I：

10.1093/nar/gkq107

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

RNA editing is a post-transcriptional modification of pre-mRNA that results in increased diversity in transcriptomes and proteomes. It occurs in a wide variety of eukaryotic organisms and in some viruses. One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation. This phenomenon has been observed in numerous transcripts, including the mammalian 5-HT(2C) receptor, which can be edited at five distinct sites. Methods used to date to quantify 5-HT(2C) receptor editing are labor-intensive, expensive and provide limited information regarding the relative abundance of 5-HT(2C) receptor editing variants. Here, we present a novel, ultra high-throughput method to quantify 5-HT(2C) receptor editing, compare it to a more conventional method, and use it to assess the effect of a range of genetic and pharmacologic manipulations on 5-HT(2C) editing. We conclude that this new method is powerful and economical, and we provide evidence that alterations in 5-HT(2C) editing appear to be a result of regional changes in brain activity, rather than a mechanism to normalize 5-HT(2C) signaling.

引用

页数：13

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