Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells.
Chemically Modified Oligonucleotides Modulate an Epigenetically Varied and Transient Form of Transcription Silencing of HIV-1 in Human Cells.
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DOI：
10.1038/mtna.2012.8
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发表时间：
2012-04-10
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影响因子：
--
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小的非编码RNA(NcRNAs)已被证明引导表观遗传沉默复合体到人类细胞中的靶点。当以基因启动子为靶点时，这些小RNA可以导致基因转录长期稳定的表观遗传沉默。到目前为止，小RNA已经被证明可以调节人类免疫缺陷病毒1型(HIV-1)和其他几个疾病相关基因的转录基因沉默(TGS)，但具体的化学作用在多大程度上可以用来产生单链骨架修饰的寡核苷酸，这一点仍然不清楚，这些寡核苷酸符合这种形式的基因靶向和调控。在这里，我们提供的数据表明，骨架修饰的特定组合可以用于产生单链反义寡核苷酸，这种单链反义寡核苷酸可以以一种独立于目标基因座表观遗传变化的方式在功能上指导HIV-1的TGS。此外，这一功能似乎取决于寡核苷酸中不存在5‘磷酸。这些数据表明，基于化学修饰的寡核苷酸方法可以作为一种以表观遗传独立的方式调节基因转录的手段来实施。
Small noncoding RNAs (ncRNAs) have been shown to guide epigenetic silencing complexes to target loci in human cells. When targeted to gene promoters, these small RNAs can lead to long-term stable epigenetic silencing of gene transcription. To date, small RNAs have been shown to modulate transcriptional gene silencing (TGS) of human immunodeficiency virus type 1 (HIV-1) as well as several other disease-related genes, but it has remained unknown as to what extent particular chemistries can be used to generate single-stranded backbone-modified oligonucleotides that are amenable to this form of gene targeting and regulation. Here, we present data indicating that specific combinations of backbone modifications can be used to generate single-stranded antisense oligonucleotides that can functionally direct TGS of HIV-1 in a manner that is however, independent of epigenetic changes at the target loci. Furthermore, this functionality appears contingent on the absence of a 5′ phosphate in the oligonucleotide. These data suggest that chemically modified oligonucleotide based approaches could be implemented as a means to regulate gene transcription in an epigenetically independent manner.
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DOI：
10.1074/jbc.m709651200
发表时间：
2008-08-22
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Suzuki K;Juelich T;Lim H;Ishida T;Watanebe T;Cooper DA;Rao S;Kelleher AD
通讯作者：
Kelleher AD
影响因子：
2.9
作者：
Beane, Randall L.;Ram, Rosalyn;Corey, David R.
通讯作者：
Corey, David R.
影响因子：
14.9
作者：
Hawkins PG;Santoso S;Adams C;Anest V;Morris KV
通讯作者：
Morris KV
影响因子：
11.4
作者：
MATZKE, MA;PRIMIG, M;MATZKE, AJM
通讯作者：
MATZKE, AJM
影响因子：
16.8
作者：
Janowski, Bethany A.;Huffman, Kenneth E.;Corey, David R.
通讯作者：
Corey, David R.