細(xì)胞的不同蛋白分子之間會(huì)通過不同的相互作用形成復(fù)雜的調(diào)控網(wǎng)絡(luò)。近年來,，細(xì)胞內(nèi)不同RNA分子之間的關(guān)系受到了越來越多的重視,。過去的研究表明長(zhǎng)的反義轉(zhuǎn)錄本會(huì)影響基因的轉(zhuǎn)錄與翻譯，但是長(zhǎng)反義轉(zhuǎn)錄本在細(xì)胞的轉(zhuǎn)錄本中很少,，相反,，編碼蛋白的RNA間短片段互補(bǔ)非常豐富。microRNA及siRNA僅約22 nt長(zhǎng),，卻能通過與目標(biāo)片段的互補(bǔ)起到重要調(diào)控基因轉(zhuǎn)錄和翻譯的作用,，那么編碼蛋白的RNA間是否存在通過短片段互補(bǔ)而相互作用的可能性呢？
健康所分子遺傳學(xué)實(shí)驗(yàn)室博士生王萍等,，在孔祥銀研究員的指導(dǎo)下,，并與巴斯大學(xué)Hurst教授合作，通過在人的24,，968個(gè)編碼蛋白的mRNA中尋找15-25 bp的互補(bǔ)區(qū),，發(fā)現(xiàn)與一系列隨機(jī)序列的比較mRNA中明顯富集短的配對(duì)；對(duì)區(qū)非隨機(jī)分布,，集于mRNA 5＇非翻譯區(qū),；且，配對(duì)區(qū)的單核苷酸多態(tài)性密度低于旁側(cè)區(qū),。這些結(jié)果表明mNA間互補(bǔ)短片段經(jīng)歷了進(jìn)化選擇,。更重要的是配對(duì)數(shù)多的mRNA的表達(dá)值較低；組織特異表達(dá)的基因中的配對(duì)顯著多于管家基因中的配對(duì),。通過與已有的小RNA的數(shù)據(jù)的比較,，并沒有發(fā)現(xiàn)mRNA間的短配對(duì)與已發(fā)現(xiàn)的小RNA有關(guān)， 提示其影響基因表達(dá)的作用并非通過產(chǎn)生小RNA實(shí)現(xiàn),。
本工作提示mRNA間很有可能通過短片段的配對(duì)相互作用,，形成基因間相互影響的網(wǎng)絡(luò)，是RNA間的一種新的相互作用機(jī)制,。這一研究結(jié)果發(fā)表在2008年的《基因組生物學(xué)》（Genome Biology）雜志上,。
該項(xiàng)工作得到了國(guó)家科技部、國(guó)家自然科學(xué)基金委和中科院項(xiàng)目的大力支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
Genome Biology 2008, 9:R169doi:10.1186/gb-2008-9-12-r169
Evidence for common short natural trans sense-antisense pairing between transcripts from protein coding genes
Ping Wang1,2 , Shanye Yin1,2 , Zhenguo Zhang1,2 , Dedong Xin1 , Landian Hu1 , Xiangyin Kong1,3 and Laurence D Hurst4
1 Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Shanghai Jiao Tong University School of Medicine (SJTUSM), 225 South Chong Qing Road, Shanghai 200025, PR China
2 Graduate School of the Chinese Academy of Sciences, 19A Yuquanlu, Beijing 100049, PR China
3 State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University, 197 Rui Jin Road II, Shanghai 200025, PR China
4 Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
Abstract
Background
There is increasing realization that regulation of genes is done partly at the RNA level by sense-antisense binding. Studies typically concentrate on the role of non-coding RNAs in regulating coding RNA. But the majority of transcripts in a cell are likely to be coding. Is it possible that coding RNA might regulate other coding RNA by short perfect sense-antisense binding? Here we compare all well-described human protein coding mRNAs against all others to identify sites 15-25 bp long that could potentially perfectly match sense-antisense.
Results
From 24,968 protein coding mRNA RefSeq sequences, none failed to find at least one match in the transcriptome. By randomizations generating artificial transcripts matched for G+C content and length, we found that there are more such trans short sense-antisense pairs than expected. Several further features are consistent with functionality of some of the putative matches. First, transcripts with more potential partners have lower expression levels, and the pair density of tissue specific genes is significantly higher than that of housekeeping genes. Further, the single nucleotide polymorphism density is lower in short pairing regions than it is in flanking regions. We found no evidence that the sense-antisense pairing regions are associated with small RNAs derived from the protein coding genes.
Conclusions
Our results are consistent with the possibility of common short perfect sense-antisense pairing between transcripts of protein coding genes.
