Post-transcriptional gene regulation has emerged as a critical control mechanism that orchestrates diverse cellular processes during germ cell differentiation. We have extensive preliminary data that demonstrate cytoplasmic Rbfox1 represses the translation of specific target mRNAs that contain (U)GCAUG elements within their 3' UTRs during specific stages of germline cyst differentiation. Through this proposal, we seek to characterize the detailed mechanisms by which cytoplasmic Rbfox1 regulates stage specific mRNA translation programs during germ cell cyst development. Our general strategy is to (1) determine what mechanisms control the unique protein expression pattern of Rbfox1 during the intermediate stages of germline cyst differentiation, prior to the onset of meiosis, (2) characterize how Rbfox1 molecularly regulates the translation of mRNA targets to achieve stage-specific translational repression and (3) characterize how Rbfox1 regulates specific mRNAs that govern early steps of germ cell development, such as pumilio and sex-lethal, and determine the extent to which ectopic expression of these targets contributes to Rbfox1 mutant phenotypes. We anticipate that these efforts will provide key insights into the translational control hierarchies that promote the development of germ cells across species.

Public Health Relevance

Understanding the unique mechanisms that govern both stem cell and germ cell activity in vivo will have a positive impact on medical science. This proposal focuses on characterizing mRNA translation programs in differentiating germ cells. We believe this work will reveal new and exciting principles in reproductive science, stem cell biology and mRNA translation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM125812-02
Application #
9610657
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Salazar, Desiree Lynn
Project Start
2018-01-01
Project End
2021-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390