Circular RNAs: Biogenesis, Function and Role in Human Diseases.
Circular RNAs: Biogenesis, Function and Role in Human Diseases.
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DOI：
10.3389/fmolb.2017.00038
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发表时间：
2017
影响因子：
5
通讯作者：
Finn SP
中科院分区：
文献类型：
--
作者：
Greene J;Baird AM;Brady L;Lim M;Gray SG;McDermott R;Finn SP
环状RNA（circRNA）目前被归类为非编码RNA（ncRNA），与线性RNA不同，它们形成共价闭合的连续环，并在哺乳动物中充当基因调控因子。它们最初被认为代表剪接错误，并且被认为丰度较低，然而，现在人们越来越认识到它们在基因调控中的重要功能。circRNA通过外显子的反向剪接或从内含子中差异产生。与线性RNA不同，通常存在于RNA分子中的3′和5′末端通过共价键连接在一起，导致环化。有趣的是，它们被发现在细胞质中是丰富的，进化上保守的和相对稳定的。这些特征赋予了circRNA许多潜在的功能，例如充当miRNA海绵，或与RNA相关蛋白结合形成调节基因转录的RNA-蛋白质复合物。已经提出，circRNA通过与miRNA相互作用在转录或转录后水平调节基因表达，并且circRNA可能在调节癌症起始和进展中的miRNA功能中起作用。与正常组织相比，circRNA似乎在肿瘤组织中更经常下调，这可能是由于（i）恶性组织中反向剪接机制的错误，（ii）肿瘤组织中失调的miRNA降解circRNA，或（iii）增加细胞增殖导致circRNA减少。已经在外泌体中鉴定出circRNA，并且最近，癌症中的染色体易位已经显示出产生与对药物治疗的抗性相关的异常融合circRNA。此外，虽然最初被认为是非编码的，但现在有越来越多的证据表明，选择的circRNA可以翻译成功能蛋白质。尽管关于circRNA生物学和基因调控机制仍有许多有待阐明，但这些ncRNA正迅速成为癌症中潜在的疾病生物标志物和治疗靶点。
Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3′ and 5′ ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization. Interestingly, they have been found to be abundant, evolutionally conserved and relatively stable in the cytoplasm. These features confer numerous potential functions to circRNAs, such as acting as miRNA sponges, or binding to RNA-associated proteins to form RNA-protein complexes that regulate gene transcription. It has been proposed that circRNA regulate gene expression at the transcriptional or post-transcriptional level by interacting with miRNAs and that circRNAs may have a role in regulating miRNA function in cancer initiation and progression. circRNAs appear to be more often downregulated in tumor tissue compared to normal tissue and this may be due to (i) errors in the back-splice machinery in malignant tissues, (ii) degradation of circRNAs by deregulated miRNAs in tumor tissue, or (iii) increasing cell proliferation leading to a reduction of circRNAs. circRNAs have been identified in exosomes and more recently, chromosomal translocations in cancer have been shown to generate aberrant fusion-circRNAs associated with resistance to drug treatments. In addition, though originally thought to be non-coding, there is now increasing evidence to suggest that select circRNAs can be translated into functional proteins. Although much remains to be elucidated about circRNA biology and mechanisms of gene regulation, these ncRNAs are quickly emerging as potential disease biomarkers and therapeutic targets in cancer.