Project Details
Description
A fundamental feature of eukaryotic life is the establishment and maintenance of cellular polarity. Molecular
motors help to establish polarity by transporting mRNAs, proteins, vesicles, and organelles to specific sites
within the cell. A variety of organisms from the single-celled yeast to humans use mRNA localization coupled
with translational regulation as a way to asymmetrically sort proteins. The prevalence of this phenomenon is
best illustrated in developing embryos, neurons and epithelial, in which thousands of mRNAs are spatially
localized. When this process is compromised, it can result in developmental and neurological disorders.
Despite the importance of this topic and the prevalence of this phenomenon, we lack a mechanistic
understanding of mRNA localization. A critical gap in our understanding pertains to how mRNAs destined for
localization are recognized by the cell and distinguished from non-localizing mRNAs. In addition to sequences
present within localizing mRNAs, the proteins that bind these mRNAs are key to their cellular fate. This
complex of proteins is responsible for linking localizing mRNAs with molecular motors and for regulating their
translation. However, identifying these critical proteins has proven to be extremely challenging. By its very
nature, the process of mRNA localization is highly dynamic. Consequently, the protein-protein and protein-RNA
interactions required for assembling localizing messenger ribonucleoprotein (mRNP) particles are weak and
transient. This has made their identification using classical biochemical approaches almost impossible; the
complex falls apart during the purification step. In this application, we propose novel strategies to address this
critical knowledge gap. The model we propose to use for these studies is the well-characterized Drosophila
melanogaster egg chamber. In Objective 1 of this application, we propose to use proximity biotin ligation to
define the core components of transport particles and to examine the conservation of these factors between
flies and mammals. In Objective 2, we propose to test the hypothesis that granular structures referred to as P
bodies coordinate the localization of mRNAs with their translational regulation.
Status | Active |
---|---|
Effective start/end date | 6/1/22 → 4/30/25 |
Funding
- National Institute of General Medical Sciences: $67,827.00
- National Institute of General Medical Sciences: $346,500.00
- National Institute of General Medical Sciences: $385,000.00
- National Institute of General Medical Sciences: $54,793.00
- National Institute of General Medical Sciences: $11,305.00
- National Institute of General Medical Sciences: $385,000.00
- National Institute of General Medical Sciences: $56,524.00
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.