The roles of TTP and BRF proteins in regulated mRNA decay.
The roles of TTP and BRF proteins in regulated mRNA decay.
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DOI：
10.1002/wrna.28
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发表时间：
2011-01
影响因子：
7.3
通讯作者：
Dixon, Dan A.
中科院分区：
文献类型：
--
作者：
Sanduja, Sandhya;Blanco, Fernando F.;Dixon, Dan A.
富金元件(ARE)是存在于转录产物3‘端非编码区的顺式作用元件，编码许多炎症和癌症相关基因。TIS11家族的RNA结合蛋白由TTP、BRF-1和BRF-2组成，在调控含ARE的mRNAs的表达中起着关键作用。通过结合和靶向含有ARE的mRNAs进行快速降解，这类RNA结合蛋白在限制一些关键基因的表达方面发挥了基础性作用，从而发挥了抗炎和抗癌的作用。TIS11家族成员的调控发生在多个水平上，通过细胞信号事件控制其转录、mRNA周转、磷酸化状态、细胞定位、与其他蛋白质的结合以及蛋白酶体降解，所有这些都影响TIS11成员促进ARE介导的mRNA衰退以及衰退非依赖性功能的能力。本文综述了TIS11家族成员对含ARE基因表达转录后调控的研究现状，并讨论了其在维持正常生理过程中的作用以及缺失时的病理后果。
AU-rich element (ARE) motifs are cis-acting elements present in the 3′UTR of mRNA transcripts that encode many inflammation- and cancer-associated genes. The TIS11 family of RNA-binding proteins, composed of TTP, BRF-1, and BRF-2 play a critical role in regulating the expression of ARE-containing mRNAs. Through their ability to bind and target ARE-containing mRNAs for rapid degradation, this class of RNA-binding proteins serves a fundamental role in limiting the expression of a number of critical genes, thereby exerting anti-inflammatory and anti-cancer effects. Regulation of TIS11 family members occurs on a number of levels through cellular signaling events to control their transcription, mRNA turnover, phosphorylation status, cellular localization, association with other proteins, and proteosomal degradation, all of which impact TIS11 members’ ability to promote ARE-mediated mRNA decay along with decay-independent functions. This review summarizes our current understanding of post-transcriptional regulation of ARE-containing gene expression by TIS11 family members and discuss their role in maintaining normal physiological processes and the pathological consequences in their absence.
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