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.