Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Cell Rep. 2012 Jul 26;2(1):111-23. doi: 10.1016/j.celrep.2012.06.003. Epub 2012 Jun 28.
Genome-wide studies have identified thousands of long noncoding RNAs (lncRNAs) lacking protein-coding capacity. However, most lncRNAs are expressed at a very low level, and in most cases there is no genetic evidence to support their in vivo function. Malat1 (metastasis associated lung adenocarcinoma transcript 1) is among the most abundant and highly conserved lncRNAs, and it exhibits an uncommon 3'-end processing mechanism. In addition, its specific nuclear localization, developmental regulation, and dysregulation in cancer are suggestive of it having a critical biological function. We have characterized a Malat1 loss-of-function genetic model that indicates that Malat1 is not essential for mouse pre- and postnatal development. Furthermore, depletion of Malat1 does not affect global gene expression, splicing factor level and phosphorylation status, or alternative pre-mRNA splicing. However, among a small number of genes that were dysregulated in adult Malat1 knockout mice, many were Malat1 neighboring genes, thus indicating a potential cis-regulatory role of Malat1 gene transcription.
全基因组研究已经鉴定出数千种缺乏编码蛋白能力的长非编码 RNA（lncRNA）。然而，大多数 lncRNA 的表达水平非常低，在大多数情况下，没有遗传证据支持它们的体内功能。Malat1（转移相关肺腺癌转录本 1）是最丰富和高度保守的 lncRNA 之一，它表现出一种不常见的 3'-末端加工机制。此外，其特定的核定位、发育调控以及在癌症中的失调表明它具有关键的生物学功能。我们已经描述了一种 Malat1 功能丧失的遗传模型，表明 Malat1 对于小鼠的产前和产后发育并非必需。此外，Malat1 的耗竭并不影响全局基因表达、剪接因子水平和磷酸化状态或选择性前体 mRNA 剪接。然而，在成年 Malat1 敲除小鼠中失调的少数基因中，许多是 Malat1 相邻基因，因此表明 Malat1 基因转录具有潜在的顺式调控作用。
