美国加州理工学院Mitchell Guttman研究团队发现，核斑周围的基因组组织驱动mRNA剪接效率。这一研究成果于2024年5月8日在线发表在国际学术期刊《自然》上。

研究人员发现与远离核斑的基因相比，定位在核斑附近的基因显示出更高的剪接体浓度、剪接体与前体mRNA的结合增加以及更高的共转录剪接水平。核斑周围的基因组织在不同细胞类型之间是动态的，核斑邻近程度的变化会导致剪接效率的差异。最后，将前体mRNA定向招募到核斑足以提高mRNA的剪接水平。

总之，这些研究结果将长期以来对核斑的观察与mRNA剪接的生物化学结合起来，证明了基因组DNA的动态三维空间组织在驱动剪接体浓度和控制mRNA剪接效率方面的关键作用。

据介绍，细胞核是高度组织化的，因此参与不同类别RNA转录和加工的因子被限制在特定的核内。核斑就是一个例子，它由高浓度的蛋白质和非编码RNA组成，是前体mRNA剪接的调控因子。目前还不清楚核斑在mRNA剪接过程中可能发挥的功能作用。

附：英文原文

Title: Genome organization around nuclear speckles drives mRNA splicing efficiency

Author: Bhat, Prashant, Chow, Amy, Emert, Benjamin, Ettlin, Olivia, Quinodoz, Sofia A., Strehle, Mackenzie, Takei, Yodai, Burr, Alex, Goronzy, Isabel N., Chen, Allen W., Huang, Wesley, Ferrer, Jose Lorenzo M., Soehalim, Elizabeth, Goh, Say-Tar, Chari, Tara, Sullivan, Delaney K., Blanco, Mario R., Guttman, Mitchell

Issue&Volume: 2024-05-08

Abstract: The nucleus is highly organized, such that factors involved in the transcription and processing of distinct classes of RNA are confined within specific nuclear bodies1,2. One example is the nuclear speckle, which is defined by high concentrations of protein and noncoding RNA regulators of pre-mRNA splicing3. What functional role, if any, speckles might play in the process of mRNA splicing is unclear4,5. Here we show that genes localized near nuclear speckles display higher spliceosome concentrations, increased spliceosome binding to their pre-mRNAs and higher co-transcriptional splicing levels than genes that are located farther from nuclear speckles. Gene organization around nuclear speckles is dynamic between cell types, and changes in speckle proximity lead to differences in splicing efficiency. Finally, directed recruitment of a pre-mRNA to nuclear speckles is sufficient to increase mRNA splicing levels. Together, our results integrate the long-standing observations of nuclear speckles with the biochemistry of mRNA splicing and demonstrate a crucial role for dynamic three-dimensional spatial organization of genomic DNA in driving spliceosome concentrations and controlling the efficiency of mRNA splicing.

DOI: 10.1038/s41586-024-07429-6

Source: https://www.nature.com/articles/s41586-024-07429-6