The mystique of epigenetic regulation: the remarkable case of a human noncoding RNA, nc886

nc886 is a regulatory noncoding RNA that is transcribed by RNA polymerase III (Pol III), is variably expressed in different biological contexts, and plays roles in inflammation and cancer. Epigenetic mechanisms play an intriguing role in regulating nc886 expression. As a maternally imprinted gene and metastable epiallele, nc866 exhibits polymorphic imprinting, with a methylation status that is influenced by environmental and biological factors. Consequently, the promoter DNA methylation status and the different resulting RNA expression levels of nc886 are associated with physiological and pathological conditions. In this review, we summarize the literature and explore the significance in relation to diverse roles of nc886. nc886 is transcribed by RNA polymerase III. nc886 binds to target proteins such as Protein Kinase R and Dicer to control their activities. nc886 has CpG islands in the promoter region, whose hypermethylation suppresses nc886 expression. CpG DNA methylation of nc886 is allele-specific. nc886 is a maternally imprinted gene. Imprinting of nc886 CpG DNA methylation is polymorphic; nc886 is imprinted in 75% of individuals but has both alleles unmethylated in the remaining 25%. nc886 is a metastable epiallele, whose CpG DNA methylation status is stochastically established and largely maintained during development. nc886 CpG DNA methylation in offspring is influenced by maternal factors including nutritional status, folic acid supplementation, age at conception and environmental factors. nc886 CpG DNA methylation is associated with several health traits. nc886 CpG DNA methylation is dysregulated in pathological conditions, with cancer being the most prominent example.

nc886是一种由RNA聚合酶III（RNA polymerase III，Pol III）转录的调控性非编码RNA（regulatory noncoding RNA），在不同生物学背景下表达水平存在差异，参与炎症反应与癌症发生过程。表观遗传机制在调控nc886的表达中发挥着引人关注的重要作用。作为一种母本印记基因（maternally imprinted gene）与易变表观等位基因（metastable epiallele），nc886表现出多态性印记模式，其甲基化状态受环境与生物学因素共同影响。因此，nc886的启动子DNA甲基化状态及其所介导的不同RNA表达水平，与生理及病理状态密切相关。在本综述中，我们系统性梳理现有文献，并探讨nc886多样生物学功能的研究价值。如前文所述，nc886由RNA聚合酶III转录。nc886可结合蛋白激酶R（Protein Kinase R）与Dicer等靶蛋白，以调控其生物活性。nc886的启动子区域存在CpG岛（CpG islands），其高甲基化状态会抑制nc886的基因表达。nc886的CpG DNA甲基化具有等位基因特异性。前文已述，nc886属于母本印记基因。nc886的CpG DNA甲基化印记具有多态性：75%的个体中nc886呈现印记状态，而剩余25%的个体中其两个等位基因均未发生甲基化。nc886是一种易变表观等位基因，其CpG DNA甲基化状态可随机建立，并在个体发育过程中大体维持稳定。子代个体的nc886 CpG DNA甲基化水平受多种母体因素影响，包括母体营养状况、叶酸补充方案、受孕年龄以及外界环境因素。nc886的CpG DNA甲基化与多种健康表型密切相关。nc886的CpG DNA甲基化在病理状态下存在失调现象，其中以癌症最为典型。