Remsburg Carolyn M, Konrad Kalin, Stepicheva Nadezda, Testa Michael, Lee Kelvin, Choe Leila, Polson Shawn, Bhavsar Jaysheel, Huang Hongzhan, Song Jia L
Department of Biological Sciences, University of Delaware, Newark, DE 19716.
Department of Neurology, Columbia University, New York, NY 10032.
Res Sq. 2023 Jun 14:rs.3.rs-3044775. doi: 10.21203/rs.3.rs-3044775/v1.
miR-31 is a highly conserved microRNA that plays critical roles in cell proliferation, migration, and differentiation. We discovered miR-31 and some of its validated targets are enriched on the mitotic spindle of the dividing sea urchin embryo and mammalian cells. Using the sea urchin embryo, we found that miR-31 inhibition led to developmental delay correlated with increased cytoskeleton and chromosomal defects. We identified miR-31 to directly suppress several actin remodeling transcripts, , and , which were localized to the mitotic spindle. miR-31 inhibition leads to increased newly translated Fascin at the spindles. Forced ectopic localization of transcripts to the cell membrane and translation led to significant developmental and chromosomal segregation defects, leading to our hypothesis that miR-31 regulates local translation at the mitotic spindle to ensure proper cell division. Furthermore, miR-31-mediated post-transcriptional regulation at the mitotic spindle may be an evolutionarily conserved regulatory paradigm of mitosis.
miR-31是一种高度保守的微小RNA,在细胞增殖、迁移和分化中发挥关键作用。我们发现miR-31及其一些已验证的靶标在分裂中的海胆胚胎和哺乳动物细胞的有丝分裂纺锤体上富集。利用海胆胚胎,我们发现抑制miR-31会导致发育延迟,这与细胞骨架和染色体缺陷增加相关。我们确定miR-31直接抑制几种肌动蛋白重塑转录本,即 和 ,它们定位于有丝分裂纺锤体。抑制miR-31会导致纺锤体上新翻译的Fascin增加。将 转录本强制异位定位到细胞膜并进行翻译会导致显著的发育和染色体分离缺陷,从而形成我们的假设,即miR-31在有丝分裂纺锤体上调节局部翻译以确保正确的细胞分裂。此外,miR-31在有丝分裂纺锤体上介导的转录后调控可能是一种进化上保守的有丝分裂调控模式。