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Post-transcriptional control of cyclin expression during cell division

Award Number: F32GM167077
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/23/2026
PERIOD OF PERFORMANCE END DATE: 12/22/2027

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Post-transcriptional control of cyclin expression during cell division - PROJECT SUMMARY: Cell division must be tightly regulated to prevent errors leading to cancer, miscarriage, and trisomy conditions. Cyclin-dependent kinases (CDKs) are master cell division regulators whose activity is switched “on” and “off” at specific phases through the binding of regulatory subunits called cyclins. Cyclin expression oscillates throughout the cell cycle due to sequential waves of synthesis and degradation. In addition to well-characterized transcription and proteolysis, evolutionarily conserved but mechanistically diverse post- transcriptional controls regulate transcript stability, localization, and translation to fine-tune cyclin expression. How post-transcriptional regulation contributes to cell cycle progression is not well-understood. In the fission yeast Schizosaccharomyces pombe the conserved cyclin Cdc13 is essential for both mitosis and meiosis. Previous work suggests that Cdc13 is controlled post-transcriptionally, but the underlying mechanisms remain undefined. I discovered that 3’UTR-dependent expression of Cdc13 is required for spore viability and proper meiotic progression but is dispensable for mitosis. The molecular mechanisms driving these phenotypes and whether additional cyclins are similarly regulated by their 3’UTRs remains unknown. The overall objective of this proposal is to determine how 3’UTRs control cyclin expression during meiotic cell division, with a focus on Cdc13. My central hypothesis is that cis-regulatory elements within 3’UTR-cdc13 recruit RNA binding protein(s) (RBPs) to control Cdc13 protein expression and ensure accurate meiotic progression. In Aim 1, I will determine how 3’UTR-dependent expression of Cdc13 controls meiotic progression using a combination of single-cell and single-molecule imaging techniques to measure Cdc13 protein and mRNA levels throughout a complete meiotic cell cycle. In Aim 2, I will identify 3’UTR region(s) and RBPs required for 3’UTR-dependent Cdc13 protein expression using a combination of single-cell quantitative fluorescent microscopy and fission yeast genetics. I will then assess RBP-RNA interactions between candidate RBPs and 3’UTR-cdc13 using complementary in vitro and in vivo biochemical assays. In Aim 3, I will build on my discovery that 3’UTR-dependent expression of an additional S. pombe cyclin, Puc1, is required for proper meiotic progression. My data support a model in which 3’UTR-dependent expression of Puc1 ensures cells complete karyogamy (nuclear fusion) prior to undergoing meiotic divisions, which is distinct from the role of 3’UTR-dependent Cdc13 expression at other meiotic stages. I will use a combination of quantitative fluorescence microscopy and genetics to test this model. Through the proposed work I will gain new hands-on training in static and timelapse quantitative fluorescent microscopy at the single-cell and single-molecule level to visualize proteins and mRNAs, respectively. I will also gain new hands-on training in a variety of RNA and protein biochemistry techniques to interrogate RBP-RNA interactions. Completion of this work will generate an experimental and conceptual framework for my future independent research program investigating how 3’UTRs control cell cycle progression in other cell types and organisms.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $76,780 )
2026	2026	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	1	6/25/2026	NEW	$76,780
														Subtotal = $76,780

Grand Total All Awards = $76,780

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Post-transcriptional control of cyclin expression during cell division

Award Number: F32GM167077

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/23/2026

PERIOD OF PERFORMANCE END DATE: 12/22/2027

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