O'Neill Michael J
Department of Molecular and Cell Biology, University of Connecticut, Storrs, 06235, USA.
Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R113-20. doi: 10.1093/hmg/ddi108.
Current research has revealed that the influence of RNA molecules on gene expression reaches beyond the realm of protein synthesis back into the nucleus, where it not only dictates the transcriptional activity of genes, but also shapes the chromatin architecture of extensive regions of DNA. Non-coding RNA, in the context of this review, refers to transcripts expressed and processed in the nucleus much like any protein coding gene, but lacking an open reading frame and often transcribed antisense to bona fide protein coding genes. In mammals, these types of transcripts are highly coincident with allele-specific silencing of imprinted genes and have a proven role in dosage compensation via X-inactivation. The biochemistry of how non-coding RNAs regulate transcription is the subject of intense research in both prokaryotic and eukaryotic models. Mechanisms such as RNA interference may have deep phylogenetic roots, but their relevance to imprinting and X-inactivation in mammals has not been proven. The remarkable diversity of non-coding transcription associated with parent-of-origin directed gene silencing hints at an equally diverse assortment of mechanisms.
当前研究表明，RNA分子对基因表达的影响不仅限于蛋白质合成领域，还延伸至细胞核，在细胞核中，它不仅决定基因的转录活性，还塑造大片段DNA的染色质结构。在本综述中，非编码RNA是指在细胞核中表达和加工的转录本，其方式与任何蛋白质编码基因类似，但缺乏开放阅读框，且常常以反义方向转录于真正的蛋白质编码基因。在哺乳动物中，这类转录本与印记基因的等位基因特异性沉默高度相关，并已证实其在X染色体失活介导的剂量补偿中发挥作用。非编码RNA如何调控转录的生物化学机制是原核生物和真核生物模型中深入研究的课题。诸如RNA干扰等机制可能具有深厚的系统发育根源，但其与哺乳动物印记和X染色体失活的相关性尚未得到证实。与亲本来源特异性基因沉默相关的非编码转录本的显著多样性暗示了同样多样的机制组合。
