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Emerging roles of alternative cleavage and polyadenylation (APA) in human disease

机译:新兴替代乳沟和角色聚腺苷酸化(APA)在人类疾病

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摘要

In the messenger RNA (mRNA) maturation process, the 3'-end of pre-mRNA is cleaved and a poly(A) sequence is added, this is an important determinant of mRNA stability and its cellular functions. More than 60%-70% of human genes have three or more polyadenylation (APA) sites and can be cleaved at different sites, generating mRNA transcripts of varying lengths. This phenomenon is termed as alternative cleavage and polyadenylation (APA) and it plays role in key biological processes like gene regulation, cell proliferation, senescence, and also in various human diseases. Loss of regulatory microRNA binding sites and interactions with RNA-binding proteins leading to APA are largely investigated in human diseases. However, the functions of the core APA machinery and related factors during disease conditions remain largely unknown. In this review, we discuss the roles of polyadenylation machinery in relation to brain disease, cardiac failure, pulmonary fibrosis, cancer, infectious conditions, and other human diseases. Collectively, we believe this review will be a useful avenue for understanding the emerging role of APA in the patho-biology of various human diseases.
机译:在信使核糖核酸(mRNA)成熟过程中,3 '端pre-mRNA裂解和聚(a)这是一个重要的序列是补充道行列式的mRNA稳定性及其细胞功能。三个或三个以上聚腺苷酸化(APA)网站,可以在不同站点被裂解,生成mRNA可变长度的记录。称为替代乳沟和聚腺苷酸化(APA)也扮演关键的角色生物过程如基因调控,细胞增殖、衰老和也不同人类疾病。结合位点与rna结合和互动蛋白质导致APA主要是调查在人类的疾病。在核心APA机械及相关因素疾病状况在很大程度上仍未知。这个审查中,我们讨论的角色聚腺苷酸化机械与大脑疾病、心脏衰竭、肺纤维化,癌症、传染病和其他人类疾病。将是一个有用的途径了解吗新兴的patho-biology APA的角色各种人类疾病。

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