Determining the Role of Me31B Protein in Germ Cell Development

Trustees Of Indiana University, Bloomington IN

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Abstract

PROJECT SUMMARY Germ cells give rise to eggs and sperm, and ultimately to a new organism of the next generation. For many animal species, germline development and germ cell formation depend on the activity of Me31B/DDX6 family RNA helicases. These helicases are believed to play critical roles in post-transcriptional RNA regulations to ensure proper spatial-temporal expression of the RNAs, which eventually leads to germline development. However, the molecular-level working mechanism of Me31B family proteins remains elusive. To study this, the PI’s research team proposes to use Drosophila Me31B as a model to address three specific knowledge gaps in our understanding of this protein: 1) What are the functionally important motifs in the Me31B protein? 2) What functions do the motifs play, and how do they contribute to Me31B’s role in germline development? 3) How is me31B expression regulated at the post-transcriptional level in the germline? The PI’s team hypothesizes that the functional motifs in Me31B play important roles in the protein’s overall activities such as regulating germline RNA stability, localization, and translation, which leads to proper germline development. To test this hypothesis, the team plans to: 1) Identify the functionally important motifs in the Me31B protein and generate novel Drosophila strains mutant for those motifs, 2) characterize the mutations’ phenotypic effects on Drosophila germline development, and 3) determine the mechanism of how me31B gene expression is regulated post-transcriptionally. These experiments will help achieve the goal of the proposed research: understanding Me31B’s in vivo working mechanism and its role in germ cell development. Knowledge obtained from the Drosophila Me31B model can be used to understand the working mechanism of the protein’s homologs in other species such as human DDX6 protein. Further, this knowledge will shed light on Me31B/DDX6’s role in human growth and development, as well as potential treatments for human disorders related to this gene/protein.