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人类顺式反义基因对、miRNAs 及其转录调控模式的综合分析。

Integrative analysis of the human cis-antisense gene pairs, miRNAs and their transcription regulation patterns.

机构信息

Bioinformatics Institute, 30 Biopolis Street #07-01, Singapore 138672, Singapore.

出版信息

Nucleic Acids Res. 2010 Jan;38(2):534-47. doi: 10.1093/nar/gkp954. Epub 2009 Nov 11.

DOI:10.1093/nar/gkp954
PMID:19906709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2811022/
Abstract

Cis-antisense gene pairs (CASGPs) can transcribe mRNAs from an opposite strand of a given locus. To classify and understand diverse CASGP phenomena in the human we compiled a genome-wide catalog of CASGPs and integrated these sequences with microarray, SAGE and miRNA data. Using the concept of overlapping regions and clustering of SA transcripts by chromosome coordinates, we identified up to 9000 overlapping antisense loci. Four thousand three hundred and seventy-four of these CASGPs form 1759 complex gene architectures. We found that approximately 35% (6347/18160) of RefSeq genes are overlapped with the antisense transcripts. About 30% of Affymetrix U133 microarray initial sequences map transcripts of approximately 35% CASGPs and reveal mostly concordant expression in CASGPs. We found strong significant overrepresentation of human miRNA genes in loci of CASGPs. We developed a data-driven model of cross-talk between co-expressed CASGPs and DICER1-mediated miRNA pathway in normal spermatogenesis and in severe teratozoospermia. Specifically, we revealed complex SA structural-functional gene module composing the protein-coding genes, WDR6, DALRD3, NDUFAF3 and ncRNA precursors, mir-425 and mir-191, which could provide downregulation of ncRNA pathway via direct targeting DICER1 and basonuclin 2 transcripts by mir-425 and mir-191 in normal spermatogenesis, but this mechanism is switched off in severe teratozoospermia. The database is available from http://globalisland.bii.a-star.edu.sg/ approximately jiangtao/sas/index3.php?link =about.

摘要

顺式反义基因对 (CASGPs) 可以从给定基因座的相反链转录 mRNA。为了对人类中的各种 CASGP 现象进行分类和理解,我们编制了一个全基因组的 CASGP 目录,并将这些序列与微阵列、SAGE 和 miRNA 数据整合在一起。使用重叠区域的概念和按染色体坐标聚类的 SA 转录本,我们鉴定了多达 9000 个重叠的反义基因座。这些 CASGPs 中有 4374 个形成了 1759 个复杂的基因结构。我们发现大约 35%(6347/18160)的 RefSeq 基因与反义转录本重叠。大约 30%的 Affymetrix U133 微阵列初始序列映射到大约 35%的 CASGP 的转录本,并在 CASGP 中显示出大多一致的表达。我们发现人类 miRNA 基因在 CASGP 基因座中高度显著过表达。我们开发了一个数据驱动的模型,用于在正常精子发生和严重畸形精子症中,共表达的 CASGP 和 DICER1 介导的 miRNA 通路之间的串扰。具体来说,我们揭示了复杂的 SA 结构-功能基因模块,该模块由蛋白质编码基因、WDR6、DALRD3、NDUFAF3 和 ncRNA 前体、mir-425 和 mir-191 组成,它可以通过 mir-425 和 mir-191 直接靶向 DICER1 和 basonuclin 2 转录物来下调 ncRNA 通路,在正常精子发生中,但在严重畸形精子症中,这种机制被关闭。该数据库可从 http://globalisland.bii.a-star.edu.sg/ 获得,网址为 approximately jiangtao/sas/index3.php?link =about。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f02/2811022/641c4f014e6a/gkp954f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f02/2811022/7bb2c11215de/gkp954f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f02/2811022/b428aa69eec1/gkp954f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f02/2811022/641c4f014e6a/gkp954f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f02/2811022/7bb2c11215de/gkp954f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f02/2811022/b428aa69eec1/gkp954f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f02/2811022/641c4f014e6a/gkp954f5.jpg

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