Poster abstracts
Poster number 147 submitted by Isabella Swafford
Programmed -1 Ribosomal Frameshifting may in part modulate miRNA function and mRNA deadenylation
Isabella Swafford (First-Year Innovation and Research Experience-FIRE, University of Maryland, College Park), Elizabeth DiCioccio (First-Year Innovation and Research Experience-FIRE, University of Maryland, College Park), Roi Turalde (First-Year Innovation and Research Experience-FIRE, University of Maryland, College Park), Adam Kellerman (First-Year Innovation and Research Experience-FIRE, University of Maryland, College Park), Vivek Advani (First-Year Innovation and Research Experience-FIRE, University of Maryland, College Park), Jonathan Dinman (Cell Biology and Molecular Genetics, University of Maryland, College Park)
Abstract:
Gene expression can be controlled at the level of mRNA stability, and recent work suggests that Programmed -1 Ribosomal Frameshifting (-1PRF), a translational recoding mechanism, consistent with this model(1)(2)(3). -1 PRF sequences are cis-acting mRNA motifs that stochastically direct elongating ribosomes to a -1 frame pre-mature termination codon (PTC, thereby destabilizing the mRNA by Nonsense Mediated mRNA Decay (NMD) pathway in eukaryotes(4)(5). There are an overwhelming majority of -1 PRF signals predicted in over 20 eukaryotic genomes, suggesting it to a universal mechanism of gene regulation(6). Here we have identified functional -1 PRF signals mRNAs encoding components of miRNA processing (DROSHA), RISC (Dicer1) and deadenylase (Ccr4-yeast and CNOT1-human) proteins harbor -1 PRF signals This observation leads to the hypothesis that miRNA function and localization and mRNA deadenylation are in part regulated by -1 PRF. Hence, dysregulation of -1 PRF and/or translational fidelity would impact global mRNA stability. These studies establish a paradigm for understanding the linkage between translational fidelity and human disease.
References:
1. Dinman JD. Mechanisms and implications of programmed translational frameshifting. Wiley Interdiscip Rev RNA Jan;3(5):661–73.
2. Belew AT, et al. Cell cycle control (and more) by programmed −1 ribosomal frameshifting: implications for disease and therapeutics. Cell Cycle. 2015
3. Belew AT, et al. Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast. Nucleic Acids Res [Internet]. 2011 Apr 1; 39(7):2799–808.
4. Jacobs JL, et al. Identification of functional, endogenous programmed -1 ribosomal frameshift signals in the genome of Saccharomyces cerevisiae. Nucleic Acids Res. 2007 Jan 12;35(1):165–74.
5. Belew AT, et al. PRFdb: a database of computationally predicted eukaryotic programmed -1 ribosomal frameshift signals. BMC Genomics. 2008 Jan;9(1):339.
Keywords: miRNA, mRNA stability, NMD