The nutrient-dependent profiling and functional characterization of ribosomal RNA modifications in mammalian cells
2025-07-23 10:49
The nutrient-dependent profiling and functional characterization of ribosomal RNA modifications in mammalian cells
Project goal: The main goal is to profile and define a nutrient-dependent rRNA modifications in mammalian cells following the amino acid deprivation condition; identify snoRNAs mediating the nutrient-dependent rRNA modifications; and characterize the roles of the nutrient-dependent rRNA modifications in survival during amino acid starvation.
Project description: This project aims to investigate how nutrient availability influences ribosomal RNA (rRNA) modifications in mammalian cells. Using direct RNA nanopore sequencing, we will profile nutrient-dependent rRNA modifications in both primary and cancer cells under amino acid starvation. We will identify the specific small nucleolar RNAs (snoRNAs) responsible for guiding these modifications and explore their functional roles through loss-of-function studies. Our research will help elucidate how ribosome structure and function adapt to nutrient stress, contributing to cellular survival and potentially uncovering new regulatory mechanisms of translation.
Expected results: We expect to identify nutrient-sensitive modifications in rRNA that vary between normal and cancer cells under amino acid starvation. Specific snoRNAs guiding these modifications will be characterized, and their functional roles in regulating translation under stress will be validated. The results may reveal novel mechanisms by which cells adapt their ribosomes to nutrient deprivation, providing insight into stress-responsive translation regulation.
Co-financing: We will use direct RNA sequencing (Oxford Nanopore) to detect rRNA modifications in cells under amino acid starvation. Comparative analyses will be performed between normal and cancer cells. Candidate snoRNAs involved in nutrient-sensitive modifications will be identified through bioinformatics and validated via knockdown experiments. Functional consequences will be assessed by examining changes in translation and cell survival under stress.