Control of translation by the nascent protein after its full synthesis and release

点击翻译按钮获取中文摘要

The centerpiece of cell survival is the proper regulation of the expression of genes, the units of DNA that carry the instructions to make proteins. Most of the known regulatory mechanisms occur at the outset of gene expression, when the synthesis of the protein is just being initiated. Thanks to the researchers' studies on how uniquely a small protein protects honeybees from bacterial infections, they realized that gene expression can also be modulated at the end of the road, when the synthesis of the encoded protein has already been completed. In this project, the researchers will investigate how widespread is this formerly unknown mechanism of gene expression regulation and will further explore the elements in the cell that guard it from working properly. The research activities will contribute to training students from high school, college, and graduate programs, as well as postdoctoral researchers. The results will be incorporated in the teaching and community service activities that the researchers conduct. The findings of the project will be communicated to the scientific community through presentations in national and international meetings and by publications in peer-reviewed journals. It has formerly been assumed that once a protein is fully synthesized, it freely diffuses from the ribosome that has produced it. However, evidence has been gathered that this is not always the case: certain proteins, whose synthesis has been thoroughly completed, linger in and interact with the ribosome, and influence the behavior of ribosomes at the translation termination stage. The behavior of proteins during their release from the ribosome may impact the expression of genes encoding other proteins. During this project, ribosome profiling (Ribo- Seq), an approach that reveals the position of translating ribosomes genome wide, will help identify the Escherichia coli genes where the end of protein synthesis is sluggish. Biochemical approaches in combination with structural studies will help elucidate the lingering interactions of the completed protein with the “mother” ribosome that modulate the termination phase of gene expression. The proposed research will advance our understanding of a previously unknown layer of translation regulation controlled by interactions between the nascent protein and the ribosome. The findings of the project may spark new ideas to control gene expression in response to variable biotic and abiotic conditions.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.