Long conserved fragments upstream of Mammalian polyadenylation sites.
Long conserved fragments upstream of Mammalian polyadenylation sites.
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DOI：
10.1093/gbe/evr053
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发表时间：
2011
影响因子：
3.3
通讯作者：
Gunderson SI
中科院分区：
文献类型：
--
作者：
Ho ES;Gunderson SI
多聚腺苷酸化是一种共转录的核RNA加工事件，涉及从RNA聚合酶中新出现的前信使RNA(Pre-mRNA)的内切，紧接着腺嘌呤核苷酸聚合，称为聚(A)尾，到多腺苷基化位点(PAS)切割的3‘端。这一看似简单的分子处理步骤已被发现与转录和剪接有关，因此增加了其调节基因表达的潜力。在这里，通过对哺乳动物顺式PAS调节元件的生物信息学分析，包括利用多个进化时间尺度的优势，我们发现意外的选择压力比先前认为的PAS要上游得多，高达200个核苷酸。引人注目的是，在人类、小鼠和牛这三个远亲哺乳动物物种的PAS侧翼区域发现了近3,000个长(30-500个核苷酸)的非编码保守片段(CFs)。当将更遥远的过渡性哺乳动物鸭嘴兽包括在内时，在保护区附近仍发现了1000多个CF。尽管这些CFs的生物学功能尚不清楚，但它们相当大的尺寸使得它们不太可能作为蛋白质识别位点，通常是≤15nt。通过利用全基因组DNaseI超敏数据，我们发现CFS的存在与染色质的可及性相关。我们的研究对于突出新的实验靶点很重要，这可能会为我们提供对多聚腺苷酸化调控方面的新理解。
Polyadenylation is a cotranscriptional nuclear RNA processing event involving endonucleolytic cleavage of the nascent, emerging pre-messenger RNA (pre-mRNA) from the RNA polymerase, immediately followed by the polymerization of adenine ribonucleotides, called the poly(A) tail, to the cleaved 3′ end of the polyadenylation site (PAS). This apparently simple molecular processing step has been discovered to be connected to transcription and splicing therefore increasing its potential for regulation of gene expression. Here, through a bioinformatic analysis of cis-PAS–regulatory elements in mammals that includes taking advantage of multiple evolutionary time scales, we find unexpected selection pressure much further upstream, up to 200 nt, from the PAS than previously thought. Strikingly, close to 3,000 long (30–500 nt) noncoding conserved fragments (CFs) were discovered in the PAS flanking region of three remotely related mammalian species, human, mouse, and cow. When an even more remote transitional mammal, platypus, was included, still over a thousand CFs were found in the proximity of the PAS. Even though the biological function of these CFs remains unknown, their considerable sizes makes them unlikely to serve as protein recognition sites, which are typically ≤15 nt. By harnessing genome wide DNaseI hypersensitivity data, we have discovered that the presence of CFs correlates with chromatin accessibility. Our study is important in highlighting novel experimental targets, which may provide new understanding about the regulatory aspects of polyadenylation.
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DOI：
10.1093/bioinformatics/btn526
发表时间：
2008-12-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Hutchins LN;Murphy SM;Singh P;Graber JH
通讯作者：
Graber JH
影响因子：
14.9
作者：
DURET, L;DORKELD, F;GAUTIER, C
通讯作者：
GAUTIER, C
影响因子：
16
作者：
Gunderson, SI;Polycarpou-Schwarz, M;Mattaj, IW
通讯作者：
Mattaj, IW
影响因子：
9.8
作者：
Ahituv N;Zhu Y;Visel A;Holt A;Afzal V;Pennacchio LA;Rubin EM
通讯作者：
Rubin EM
影响因子：
56.9
作者：
Gibbs, Richard A.;Rogers, Jeffrey;Zwieg, Ann S.
通讯作者：
Zwieg, Ann S.