Genome Biology：mRNA间调控网络的研究

细胞的不同蛋白分子之间会通过不同的相互作用形成复杂的调控网络。近年来，细胞内不同RNA分子之间的关系受到了越来越多的重视。过去的研究表明长的反义转录本会影响基因的转录与翻译，但是长反义转录本在细胞的转录本中很少，相反，编码蛋白的RNA间短片段互补非常丰富。microRNA及siRNA仅约22 nt长，却能通过与目标片段的互补起到重要调控基因转录和翻译的作用，那么编码蛋白的RNA间是否存在通过短片段互补而相互作用的可能性呢？
健康所分子遗传学实验室博士生王萍等，在孔祥银研究员的指导下，并与巴斯大学Hurst教授合作，通过在人的24，968个编码蛋白的mRNA中寻找15-25 bp的互补区，发现与一系列随机序列的比较mRNA中明显富集短的配对；对区非随机分布，集于mRNA 5＇非翻译区；且，配对区的单核苷酸多态性密度低于旁侧区。这些结果表明mNA间互补短片段经历了进化选择。更重要的是配对数多的mRNA的表达值较低；组织特异表达的基因中的配对显著多于管家基因中的配对。通过与已有的小RNA的数据的比较，并没有发现mRNA间的短配对与已发现的小RNA有关， 提示其影响基因表达的作用并非通过产生小RNA实现。
本工作提示mRNA间很有可能通过短片段的配对相互作用，形成基因间相互影响的网络，是RNA间的一种新的相互作用机制。这一研究结果发表在2008年的《基因组生物学》（Genome Biology）杂志上。
该项工作得到了国家科技部、国家自然科学基金委和中科院项目的大力支持。（生物谷Bioon.com）
生物谷推荐原始出处：
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 China2 Graduate School of the Chinese Academy of Sciences, 19A Yuquanlu, Beijing 100049, PR China3 State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University, 197 Rui Jin Road II, Shanghai 200025, PR China4 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.