Structure and function of pre-mRNA 5'-end capping quality control and 3'-end processing.
Structure and function of pre-mRNA 5'-end capping quality control and 3'-end processing.
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DOI：
10.1021/bi401715v
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发表时间：
2014-04-01
期刊：
影响因子：
2.9
通讯作者：
Tong L
中科院分区：
文献类型：
--
作者：
Jurado AR;Tan D;Jiao X;Kiledjian M;Tong L
信使RNA前体(Pre-mRNAs)是真核生物中RNA聚合酶II(POL II)的新生转录产物，必须经过广泛的成熟加工，包括5‘端封端、剪接、3’端切割和多聚腺苷化。本文将综述过去几年来关于大多数前mRNA3‘端处理所需的大型机制以及复制依赖的组蛋白前mRNA3’端处理的不同机制的结构和功能信息，这些信息为了解这些机制中的蛋白质及其亚复合体提供了很好的见解。结构和生化研究也导致了一类新的酶(DXO家族酶)的鉴定，这些酶对5‘端封端途径的中间体具有活性。功能研究表明，这些酶是一种新的质量监测机制的前mRNA 5‘端封顶的一部分。不完全封顶的前-mRNAs是在酵母和人类细胞中产生的，而该领域的普遍看法是封顶总是进行到完成，不完全封顶会导致人类细胞中的剪接和3‘端切割缺陷。DXO家族酶是检测和降解这些有缺陷的RNA所必需的。
Messenger RNA precursors (pre-mRNAs) are produced as the nascent transcripts of RNA polymerase II (Pol II) in eukaryotes and must undergo extensive maturational processing, including 5′-end capping, splicing, and 3′-end cleavage and polyadenylation. This review will summarize the structural and functional information reported over the past few years on the large machinery required for the 3′-end processing of most pre-mRNAs, as well as the distinct machinery for the 3′-end processing of replication-dependent histone pre-mRNAs, which have provided great insights into the proteins and their subcomplexes in these machineries. Structural and biochemical studies have also led to the identification of a new class of enzymes (the DXO family enzymes) with activity toward intermediates of the 5′-end capping pathway. Functional studies demonstrate that these enzymes are part of a novel quality surveillance mechanism for pre-mRNA 5′-end capping. Incompletely capped pre-mRNAs are produced in yeast and human cells, in contrast to the general belief in the field that capping always proceeds to completion, and incomplete capping leads to defects in splicing and 3′-end cleavage in human cells. The DXO family enzymes are required for the detection and degradation of these defective RNAs.