Collaborative Regulation of Translational Targets by the ARF and NF1 Tumor Suppressors
Abstract
The regulation of mRNA loading onto polysomes is an understudied area of NF1 tumor cell biology and we are poised to take advantage of the model system provided by Nf1/Arf-deficient mouse Schwann cells. This will allow us to identify which mRNAs are associated with polysomes to understand the mechanism of how mRNAs are preferentially loaded onto or unloaded from ribosomes in cells lacking Nf1 and Arf. There were three major milestones for this grant proposal: 1) identify mRNAs whose translation rates are lower or higher in each Schwann cell background, 2) determine motifs in untranslated regions of each mRNA responsible for translation, and 3) identify proteins bound to these mRNAs. Ribosome protection and RNA sequencing revealed 27-downregulatedmRNAs and 41-upregulated mRNAs in Nf1fl/fl/Arffl/fl Schwann cells. Alignment of these mRNAs revealed very few consistent regions or motifs of interest. RNA pulldown experiments revealed numerous proteins, namely a class of RNA helicases, was bound to many of the mRNAs being translated more efficiently.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1216078
Entities
People
- Jason D Weber
Organizations
- Washington University in St. Louis