Overexpression of MLN51 triggers P-body disassembly and formation of a new type of RNA granules
Overexpression of MLN51 triggers P-body disassembly and formation of a new type of RNA granules
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DOI：
10.1242/jcs.154500
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发表时间：
2014-11-01
影响因子：
4
通讯作者：
Gillet, Reynald
中科院分区：
文献类型：
--
作者：
Cougot, Nicolas;Daguenet, Elisabeth;Gillet, Reynald
转移性淋巴结51（MLN 51，也称为CASC 3）是外显子连接复合物（EJC）的核心组分，其加载到剪接的mRNA上并在决定其命运中起重要作用。与其他三种EJC核心组分[eIF 4AIII，Magoh和Y14（也称为RBM 8A）]不同，MLN 51主要位于细胞质中，在应激颗粒的组装中起关键作用。在这项研究中，我们进一步研究了MLN 51的细胞质作用。我们表明，MLN 51是一个新的组成部分的加工机构（P-机构）。当过表达时，MLN 51定位于新的小细胞质病灶中。这些含有RNA，显示定向运动，并与应激颗粒和P体不同。这些病灶的出现与P体解体的过程有关。在过表达MLN 51的人HER 2阳性（HER 2（+））乳腺癌细胞中也观察到类似的P体计数减少。这表明P体分解和随后的mRNA失调可能与癌症进展相关。
Metastatic lymph node 51 (MLN51, also known as CASC3) is a core component of the exon junction complex (EJC), which is loaded onto spliced mRNAs and plays an essential role in determining their fate. Unlike the three other EJC core components [eIF4AIII, Magoh and Y14 (also known as RBM8A)], MLN51 is mainly located in the cytoplasm, where it plays a key role in the assembly of stress granules. In this study, we further investigated the cytoplasmic role of MLN51. We show that MLN51 is a new component of processing bodies (P-bodies). When overexpressed, MLN51 localizes in novel small cytoplasmic foci. These contain RNA, show directed movements and are distinct from stress granules and P-bodies. The appearance of these foci correlates with the process of P-body disassembly. A similar reduction in P-body count is also observed in human HER2-positive (HER2(+)) breast cancer cells overexpressing MLN51. This suggests that P-body disassembly and subsequent mRNA deregulation might correlate with cancer progression.