Identification of a consensus element recognized and cleaved by IRE1 alpha.
Identification of a consensus element recognized and cleaved by IRE1 alpha.
复制标题
DOI：
10.1093/nar/gkq452
复制
发表时间：
2010-10
影响因子：
14.9
通讯作者：
Iwawaki T
中科院分区：
文献类型：
--
作者：
Oikawa D;Tokuda M;Hosoda A;Iwawaki T
IRE1α是一种位于内质网（ER）的跨膜rna酶，在内质网应激反应中起核心作用。在内质网胁迫下，IRE1α被激活，并在编码转录因子x- box结合蛋白1 （XBP1）的mRNA中切割特定的外显子-内含子位点。此外，先前的研究使我们能够预测IRE1α靶向XBP1以外的几种rna。事实上，我们已经确定CD59 mRNA是IRE1α的切割靶点。然而，目前尚不清楚IRE1α如何识别和切割目标rna。为了解决这个问题，我们设计了一种独特的方法，将体外切割实验与外显子微阵列分析相结合，并对IRE1α切割靶点进行全基因组筛选。我们确定了13个新的mrna作为候选IRE1α切割靶点。此外，对新的切割位点的分析揭示了一个共识序列（CUGCAG），当伴随着茎环结构时，它对ire1 α-介导的切割至关重要。该序列和结构在已知的IRE1α裂解靶点CD59和XBP1中也是保守的。这些发现为理解IRE1α识别和切割靶rna的分子机制提供了重要线索。
IRE1α is an endoplasmic reticulum (ER)-located transmembrane RNase that plays a central role in the ER stress response. Upon ER stress, IRE1α is activated and cleaves specific exon–intron sites in the mRNA encoding the transcription factor X-box-binding protein 1 (XBP1). In addition, previous studies allow us to predict that IRE1α targets several RNAs other than the XBP1. In fact, we have identified CD59 mRNA as a cleavage target of IRE1α. However, it is not yet clear how IRE1α recognizes and cleaves target RNAs. To address this question, we devised a unique method that combines an in vitro cleavage assay with an exon microarray analysis, and performed genome-wide screening for IRE1α cleavage targets. We identified 13 novel mRNAs as candidate IRE1α cleavage targets. Moreover, an analysis of the novel cleavage sites revealed a consensus sequence (CUGCAG) which, when accompanied by a stem-loop structure, is essential for IRE1α-mediated cleavage. The sequence and structure were also conserved in the known IRE1α cleavage targets, CD59 and XBP1. These findings provide the important clue to understanding the molecular mechanisms by which IRE1α recognizes and cleaves target RNAs.
登录
查看更多内容
影响因子：
64.5
作者：
Yoshida, H;Matsui, T;Mori, K
通讯作者：
Mori, K
影响因子：
64.5
作者：
Sidrauski, C;Walter, P
通讯作者：
Walter, P
影响因子：
11.4
作者：
Wang, XZ;Harding, HP;Ron, D
通讯作者：
Ron, D
影响因子：
64.8
作者：
Calfon, M;Zeng, HQ;Ron, D
通讯作者：
Ron, D
影响因子：
4.5
作者：
Shen X;Ellis RE;Sakaki K;Kaufman RJ
通讯作者：
Kaufman RJ