Malat1 is not an essential component of nuclear speckles in mice
Malat1 is not an essential component of nuclear speckles in mice
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DOI：
10.1261/rna.033217.112
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发表时间：
2012-08-01
期刊：
影响因子：
4.5
通讯作者：
Prasanth, Kannanganattu V.
中科院分区：
文献类型：
--
作者：
Nakagawa, Shinichi;Ip, Joanna Y.;Prasanth, Kannanganattu V.
Malat 1是一种丰富的长非编码RNA，定位于称为核斑点的核体，其中包含一组独特的前mRNA加工因子。先前在细胞培养中的研究表明，Malat 1与前mRNA剪接因子相互作用，包括富含丝氨酸和丝氨酸的蛋白质（SR）家族，并调节各种生物学过程，包括癌细胞迁移，突触形成，细胞周期进展和对血清刺激的反应。为了解决Malat 1在活生物体中的生理功能，我们使用同源重组产生Malat 1敲除（KO）小鼠。出乎意料的是，Malat 1-KO小鼠是可行的和可生育的，没有表现出明显的表型。核斑点标记物也正确地定位在缺乏Malat 1的细胞中。然而，另一种长的非编码RNA-Neat 1的细胞水平-它是称为paraspeckles的核小体的结构组成部分-在缺乏Malat 1的特定组织和细胞中下调。我们认为Malat 1在正常实验室条件下维持的活小鼠中不是必需的，并且其功能仅在特定细胞类型和特定条件下才变得明显。
Malat1 is an abundant long, noncoding RNA that localizes to nuclear bodies known as nuclear speckles, which contain a distinct set of pre-mRNA processing factors. Previous studies in cell culture have demonstrated that Malat1 interacts with pre-mRNA splicing factors, including the serine-and arginine-rich (SR) family of proteins, and regulates a variety of biological processes, including cancer cell migration, synapse formation, cell cycle progression, and responses to serum stimulation. To address the physiological function of Malat1 in a living organism, we generated Malat1-knockout (KO) mice using homologous recombination. Unexpectedly, the Malat1-KO mice were viable and fertile, showing no apparent phenotypes. Nuclear speckle markers were also correctly localized in cells that lacked Malat1. However, the cellular levels of another long, noncoding RNA-Neat1-which is an architectural component of nuclear bodies known as paraspeckles, were down-regulated in a particular set of tissues and cells lacking Malat1. We propose that Malat1 is not essential in living mice maintained under normal laboratory conditions and that its function becomes apparent only in specific cell types and under particular conditions.