The structure-function relationship of the nucleus is tightly regulated, especially during heat shock. Typically, heat shock activates molecular chaperones that prevent protein misfolding and preserve genome integrity. However, the molecular mechanisms that regulate nuclear structure-function relationships during heat shock remain unclear. Here, we show that lamin A and C (hereafter lamin A/C; both lamin A and C are encoded by LMNA) are required for heat-shock-mediated transcriptional induction of the Hsp70 gene locus (HSPA genes). Interestingly, lamin A/C regulates redistribution of nuclear myosin I (NM1) into the nucleus upon heat shock, and depletion of either lamin A/C or NM1 abrogates heat-shock-induced repositioning of Hsp70 gene locus away from the nuclear envelope. Lamins and NM1 also regulate spatial positioning of the SC35 (also known as SRSF2) speckles - important nuclear landmarks that modulates Hsp70 gene locus expression upon heat shock. This suggests an intricate crosstalk between nuclear lamins, NM1 and SC35 organization in modulating transcriptional responses of the Hsp70 gene locus during heat shock. Taken together, this study unravels a novel role for lamin A/C in the regulation of the spatial dynamics and function of the Hsp70 gene locus upon heat shock, via the nuclear motor protein NM1.This article has an associated First Person interview with the first author of the paper.

中文翻译：

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Lamin A/C 通过核肌球蛋白 I 调节 Hsp70 基因座的空间组织和功能。

细胞核的结构-功能关系受到严格调控，尤其是在热激期间。通常，热休克会激活分子伴侣，防止蛋白质错误折叠并保持基因组完整性。然而，热激过程中调节核结构与功能关系的分子机制仍不清楚。在这里，我们表明核纤层蛋白 A 和 C（以下简称核纤层蛋白 A/C；核纤层蛋白 A 和 C 均由 LMNA 编码）是热休克介导的 Hsp70 基因座（HSPA 基因）转录诱导所必需的。有趣的是，核纤层蛋白 A/C 在热休克时调节核肌球蛋白 I (NM1) 重新分布到细胞核中，而核纤层蛋白 A/C 或 NM1 的耗竭会消除热休克诱导的 Hsp70 基因位点远离核膜的重新定位。核纤层蛋白和 NM1 还调节 SC35（也称为 SRSF2）斑点的空间定位，SC35 斑点是在热激时调节 Hsp70 基因位点表达的重要核标志。这表明核纤层蛋白、NM1 和 SC35 组织之间存在复杂的串扰，以调节热休克期间 Hsp70 基因座的转录反应。总而言之，这项研究揭示了核纤层蛋白 A/C 在热休克时通过核马达蛋白 NM1 调节 Hsp70 基因座的空间动力学和功能中的新作用。本文有相关的第一人称采访论文作者。