Post-transcriptional regulation during mitosis

有丝分裂期间的转录后调控

• 批准号: 2103453
• 负责人: Jia Song
• 金额: $ 95万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2103453&HistoricalAwards=false
• 关键词: Post; transcriptional; regulation; during; mitosis

The project examines regulation of cell division, or mitosis, which is a critical biological process used by all organisms. The newly fertilized egg must undergo rapid cell divisions to form embryonic structures. The main purpose of cell division in early embryonic development is to duplicate chromosomes and separate them faithfully and equally into two cells. Without proper regulation of cell divisions, embryos can end up with cells with lost identities, cells with aberrant numbers of chromosomes that can lead to genetic disorders, and birth defects. The project investigates how regulatory RNAs mediate mitosis, by controlling where and when proteins important for cell division are made within cells of the early embryo. Overall, this project will contribute to a deeper understanding of the fundamental process of cell division, which will in turn promote our understanding of cell function and of normal embryo development and birth defects. The PI also proposes education activities that build upon the proposed research project. The PI develops an undergraduate experimental laboratory course that is a student-driven, inquiry-based lab where students will take ownership of their project and directly contribute to the PI's research. The goal of this laboratory course is to expose a greater number of undergraduate students to an authentic research experience in order to encourage students to enter and stay in STEM fields. Additionally, the PI collaborates with early childhood educators to foster scientific interest in young children. The proposed educational activities incorporate the PI's expertise in cell and developmental biology with ongoing research collaborations. Cell division is a fundamental and highly regulated cellular process used by all eukaryotic cells and organisms. The project goal is to examine how post-transcriptional regulation mediated by microRNAs (miRNAs) controls local translation in order to fine-tune mitosis. In cleavage-stage embryos, cells undergo rapid cell divisions, alternating between DNA synthesis and mitotic phases of the cell cycle. During mitosis, chromosomal segregation is mediated by the mitotic spindle, which is a highly dynamic structure composed of cytoskeletal proteins and hundreds of other proteins that regulate this carefully choreographed process. Results indicate that in sea urchins, an evolutionarily conserved miRNA, miR-31, and some of its target transcripts have cell cycle-dependent dynamic distribution: They are in the perinuclear region of non-dividing cells, and they are enriched on the mitotic spindles in dividing cells of embryos. This novel and striking oscillating localization of miR-31 and its target RNA transcripts leads to the overarching hypothesis that miR-31 regulates mitosis. This research will test the sub-hypotheses that: 1) miR-31 regulates cytoskeletal transcripts to modulate microtubule dynamics; 2) miR-31 controls local translation during mitosis; and 3) miR-31 targets are stabilized and transported by RNA-binding proteins. By examining the large blastomeres of sea urchin embryos, cell and molecular techniques, and high-resolution imaging, the PI will examine how miR-31 mediates the fast growth and shrinkage of microtubules in choreographing mitosis. The project will contribute to a mechanistic understanding of mitosis and reveal a novel and evolutionarily conserved mechanism of miRNA-mediated regulation during mitosis. This project is jointly funded by the Cellular Dynamics and Function program and the Genetic Mechanisms program of the Molecular and Cellular Biosciences Division in the Biological Sciences Directorate.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该项目研究细胞分裂或有丝分裂的调节，这是所有生物体使用的关键生物过程。 新的受精卵必须经历快速的细胞分裂以形成胚胎结构。 在早期胚胎发育中，细胞分裂的主要目的是复制染色体，并将它们忠实地均等地分成两个细胞。 如果没有适当的细胞分裂调节，胚胎最终可能会失去身份，染色体数量异常的细胞，从而导致遗传疾病和出生缺陷。 该项目研究了调控RNA如何通过控制早期胚胎细胞内对细胞分裂重要的蛋白质在何时何地产生来介导有丝分裂。 总的来说，该项目将有助于更深入地了解细胞分裂的基本过程，这反过来又将促进我们对细胞功能以及正常胚胎发育和出生缺陷的理解。 PI还建议在拟议研究项目的基础上开展教育活动。 PI开发了一个本科实验室课程，这是一个学生驱动的，基于探究的实验室，学生将拥有他们的项目，并直接为PI的研究做出贡献。 本实验室课程的目标是让更多的本科生接触到真实的研究经验，以鼓励学生进入并留在STEM领域。 此外，PI与幼儿教育工作者合作，培养幼儿的科学兴趣。 拟议的教育活动将PI在细胞和发育生物学方面的专业知识与正在进行的研究合作相结合。 细胞分裂是所有真核细胞和生物体使用的基本和高度调节的细胞过程。 该项目的目标是研究microRNAs（miRNAs）介导的转录后调节如何控制局部翻译，以微调有丝分裂。 在卵裂期胚胎中，细胞经历快速的细胞分裂，在细胞周期的DNA合成和有丝分裂阶段之间交替。 在有丝分裂期间，染色体分离由有丝分裂纺锤体介导，有丝分裂纺锤体是一种高度动态的结构，由细胞骨架蛋白和数百种调节这一精心设计的过程的其他蛋白质组成。 结果表明，在海胆中，一种进化上保守的miRNA，miR-31，和它的一些靶转录物具有细胞周期依赖的动态分布：它们在非分裂细胞的核周区域，并且它们富集在胚胎分裂细胞的有丝分裂纺锤体上。 miR-31及其靶RNA转录物的这种新颖和惊人的振荡定位导致了miR-31调节有丝分裂的总体假设。 本研究将测试以下子假设：1）miR-31调节细胞骨架转录物以调节微管动力学; 2）miR-31控制有丝分裂期间的局部翻译; 3）miR-31靶标通过RNA结合蛋白稳定和转运。 通过检查海胆胚胎的大卵裂球，细胞和分子技术以及高分辨率成像，PI将研究miR-31如何介导微管在编排有丝分裂中的快速生长和收缩。 该项目将有助于有丝分裂的机制理解，并揭示有丝分裂期间miRNA介导的调控的新的和进化上保守的机制。 该项目由生物科学理事会分子和细胞生物科学部的细胞动力学和功能计划以及遗传机制计划共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

RNA localization to the mitotic spindle is essential for early development and is regulated by kinesin-1 and dynein.

RNA 定位到有丝分裂纺锤体对于早期发育至关重要，并受到驱动蛋白-1 和动力蛋白的调节。

• DOI: 10.1242/jcs.260528
• 发表时间: 2023
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Remsburg,CarolynM;Konrad,KalinD;Song,JiaL
• 通讯作者: Song,JiaL

microRNA-124 regulates Notch and NeuroD1 to mediate transition states of neuronal development.

• DOI: 10.1002/dneu.22902
• 发表时间: 2023-01
• 期刊: Developmental neurobiology
• 影响因子: 3

The actin bundling protein Fascin is important for proper early development in Strongylocentrotus purpuratus embryos.

• DOI: 10.17912/micropub.biology.000717
• 发表时间: 2023
• 期刊: microPublication biology
• 作者: Testa, Michael D;Remsburg, Carolyn M;Song, Jia L
• 通讯作者: Song, Jia L