Impact of host genes and strand selection on miRNA and miRNA* expression.
Impact of host genes and strand selection on miRNA and miRNA* expression.
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DOI：
10.1371/journal.pone.0023854
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Bortoluzzi S
中科院分区：
文献类型：
--
作者：
Biasiolo M;Sales G;Lionetti M;Agnelli L;Todoerti K;Bisognin A;Coppe A;Romualdi C;Neri A;Bortoluzzi S
miRNAs表达的失调在遗传、多因素疾病和人类癌症的发病机制中起关键作用。我们利用序列、基因组和表达信息研究了miRNA生物发生中转录后调控的两个主要方面，即链选择调控和基因内miRNA与宿主基因之间的表达关系。我们考虑了在五个相当大的微阵列数据集中测量的miRNAs表达谱，包括来自不同正常细胞类型和组织以及不同肿瘤和疾病状态的样本。首先，对“姐妹”miRNA对（miRNA/miRNA*，相同发夹前体的5′和3′链）的表达谱的研究表明，链选择受到高度调控，因为它显示组织/细胞/条件特异性调节。我们使用有关链选择偏差的方向和强度的信息对样本分类进行无监督聚类分析，证明能够区分不同的组织，有时区分正常细胞和恶性细胞。然后，考虑到最小表达阈值，在少数miRNA对中，只有一种成熟的miRNA总是存在于所有考虑的细胞类型中，而大多数对在一些细胞类型中同时表达，或者在其他细胞类型中同时表达。在相当一部分同时表达的基因对中，在相当水平上发现的主要和次要形式可能有助于转录后基因沉默，可能是以协调的方式。在研究的第二部分中，通过表达谱检测，基因内miRNAs和它们的“宿主”mRNA基因的共表达的表现倾向被推翻，这表明给定宿主基因的表达谱很难作为共转录的miRNAs用于转录后调控网络推断的良好估计。我们的研究结果指出了miRNA生物合成的转录后阶段的调节重要性，加强了miRNA生物合成的这种层在基于miRNA的细胞活性调节中的作用。
Dysregulation of miRNAs expression plays a critical role in the pathogenesis of genetic, multifactorial disorders and in human cancers. We exploited sequence, genomic and expression information to investigate two main aspects of post-transcriptional regulation in miRNA biogenesis, namely strand selection regulation and expression relationships between intragenic miRNAs and host genes. We considered miRNAs expression profiles, measured in five sizeable microarray datasets, including samples from different normal cell types and tissues, as well as different tumours and disease states. First, the study of expression profiles of “sister” miRNA pairs (miRNA/miRNA*, 5′ and 3′ strands of the same hairpin precursor) showed that the strand selection is highly regulated since it shows tissue-/cell-/condition-specific modulation. We used information about the direction and the strength of the strand selection bias to perform an unsupervised cluster analysis for the sample classification evidencing that is able to distinguish among different tissues, and sometimes between normal and malignant cells. Then, considering a minimum expression threshold, in few miRNA pairs only one mature miRNA is always present in all considered cell types, whereas the majority of pairs were concurrently expressed in some cell types and alternatively in others. In a significant fraction of concurrently expressed pairs, the major and the minor forms found at comparable levels may contribute to post-transcriptional gene silencing, possibly in a coordinate way. In the second part of the study, the behaved tendency to co-expression of intragenic miRNAs and their “host” mRNA genes was confuted by expression profiles examination, suggesting that the expression profile of a given host gene can hardly be a good estimator of co-transcribed miRNA(s) for post-transcriptional regulatory networks inference. Our results point out the regulatory importance of post-transcriptional phases of miRNAs biogenesis, reinforcing the role of such layer of miRNA biogenesis in miRNA-based regulation of cell activities.
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影响因子：
3.7
作者：
Corcoran DL;Pandit KV;Gordon B;Bhattacharjee A;Kaminski N;Benos PV
通讯作者：
Benos PV
影响因子：
--
作者：
Jin W;Grant JR;Stothard P;Moore SS;Guan LL
通讯作者：
Guan LL
影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
7
作者：
Gennarino, Vincenzo Alessandro;Sardiello, Marco;Banfi, Sandro
通讯作者：
Banfi, Sandro
DOI：
10.1073/pnas.0812591106
发表时间：
2009-02-03
影响因子：
11.1
作者：
Jazdzewski, Krystian;Liyanarachchi, Sandya;De la Chapelle, Albert
通讯作者：
De la Chapelle, Albert