Stowers Institute for Medical Research, Kansas City, MO, USA.
EMBO Rep. 2023 Jan 9;24(1):e55345. doi: 10.15252/embr.202255345. Epub 2022 Nov 10.
Paraspeckles are subnuclear RNA-protein structures that are implicated in important processes including cellular stress response, differentiation, and cancer progression. However, it is unclear how paraspeckles impart their physiological effect at the molecular level. Through biochemical analyses, we show that paraspeckles interact with the SWI/SNF chromatin-remodeling complex. This is specifically mediated by the direct interaction of the long-non-coding RNA NEAT1 of the paraspeckles with ARID1B of the cBAF-type SWI/SNF complex. Strikingly, ARID1B depletion, in addition to resulting in loss of interaction with the SWI/SNF complex, decreases the binding of paraspeckle proteins to chromatin modifiers, transcription factors, and histones. Functionally, the loss of ARID1B and NEAT1 influences the transcription and the alternative splicing of a common set of genes. Our findings reveal that dynamic granules such as the paraspeckles may leverage the specificity of epigenetic modifiers to impart their regulatory effect, thus providing a molecular basis for their function.
核旁斑点是核内 RNA-蛋白质结构，参与包括细胞应激反应、分化和癌症进展等重要过程。然而，核旁斑点如何在分子水平上发挥其生理效应尚不清楚。通过生化分析，我们表明核旁斑点与 SWI/SNF 染色质重塑复合物相互作用。这是由核旁斑点的长链非编码 RNA NEAT1 与 cBAF 型 SWI/SNF 复合物的 ARID1B 的直接相互作用特异性介导的。引人注目的是，ARID1B 的耗竭除了导致与 SWI/SNF 复合物的相互作用丧失外，还降低了核旁斑点蛋白与染色质修饰物、转录因子和组蛋白的结合。功能上，ARID1B 和 NEAT1 的缺失影响一组常见基因的转录和可变剪接。我们的发现表明，像核旁斑点这样的动态颗粒可能利用表观遗传修饰物的特异性来发挥其调节作用，从而为其功能提供了分子基础。
