High SINE RNA Expression Correlates with Post-Transcriptional Downregulation of BRCA1.

High SINE RNA Expression Correlates with Post-Transcriptional Downregulation of BRCA1.
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DOI:
10.3390/genes4020226
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发表时间:
2013-04-29
期刊:
影响因子:
3.5
通讯作者:
Bosco G
Bosco G
中科院分区:
生物学3区
文献类型:
--
作者:
Peterson M;Chandler VL;Bosco G

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短穿插核素(SINES)是一种非自主反转录转座子,构成了人类基因组的很大一部分。Sine在人类疾病中是去甲基化的,但Sine是否会被转录诱导,以及由此产生的转录物可能如何影响蛋白质编码基因的表达尚不清楚。在这里,我们证明了肿瘤抑制基因BRCA1的mRNA下调与Sine的转录增加以及正义和反义Sine小RNA的产生有关。我们发现BRCA1 mRNA在转录后下调,这是一种DICER和DROSHA依赖的方式,并且与BRCA1内含子序列相同的正弦反向重复序列的表达足以下调BRCA1 mRNA。这些观察结果表明,Sine的转录激活可能有助于RNA介导的人类基因转录后沉默的一种新机制。
Short Interspersed Nuclear Elements (SINEs) are non-autonomous retrotransposons that comprise a large fraction of the human genome. SINEs are demethylated in human disease, but whether SINEs become transcriptionally induced and how the resulting transcripts may affect the expression of protein coding genes is unknown. Here, we show that downregulation of the mRNA of the tumor suppressor gene BRCA1 is associated with increased transcription of SINEs and production of sense and antisense SINE small RNAs. We find that BRCA1 mRNA is post-transcriptionally down-regulated in a Dicer and Drosha dependent manner and that expression of a SINE inverted repeat with sequence identity to a BRCA1 intron is sufficient for downregulation of BRCA1 mRNA. These observations suggest that transcriptional activation of SINEs could contribute to a novel mechanism of RNA mediated post-transcriptional silencing of human genes.
DOI: 10.1093/jnci/53.3.661
发表时间: 1974-01-01
期刊: JOURNAL OF THE NATIONAL CANCER INSTITUTE
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