鉴定 MALAT-1 非编码 RNA 定位于核斑的顺式和反式作用因子。
Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles.
机构信息
Radioisotope Center, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
出版信息
RNA. 2012 Apr;18(4):738-51. doi: 10.1261/rna.028639.111. Epub 2012 Feb 21.
Abstract
MALAT-1 noncoding RNA is localized to nuclear speckles despite its mRNA-like characteristics. Here, we report the identification of several key factors that promote the localization of MALAT-1 to nuclear speckles and also provide evidence that MALAT-1 is involved in the regulation of gene expression. Heterokaryon assays revealed that MALAT-1 does not shuttle between the nucleus and cytoplasm. RNAi-mediated repression of the nuclear speckle proteins, RNPS1, SRm160, or IBP160, which are well-known mRNA processing factors, resulted in the diffusion of MALAT-1 to the nucleoplasm. We demonstrated that MALAT-1 contains two distinct elements directing transcripts to nuclear speckles, which were also capable of binding to RNPS1 in vitro. Depletion of MALAT-1 represses the expression of several genes. Taken together, our results suggest that RNPS1, SRm160, and IBP160 contribute to the localization of MALAT-1 to nuclear speckles, where MALAT-1 could be involved in regulating gene expression.
摘要
MALAT-1 非编码 RNA 尽管具有 mRNA 样的特征，但定位于核斑。在这里，我们报告了几个促进 MALAT-1 定位于核斑的关键因素的鉴定，并提供了 MALAT-1 参与基因表达调控的证据。杂种核试验表明 MALAT-1 不会在核和细胞质之间穿梭。RNAi 介导的核斑蛋白 RNPS1、SRm160 或 IBP160 的抑制，这些都是众所周知的 mRNA 加工因子，导致 MALAT-1 扩散到核质。我们证明 MALAT-1 包含两个将转录本导向核斑的不同元件，这两个元件也能够在体外与 RNPS1 结合。MALAT-1 的耗竭会抑制几个基因的表达。总之，我们的结果表明，RNPS1、SRm160 和 IBP160 有助于 MALAT-1 定位于核斑，MALAT-1 可能参与调节基因表达。
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