Poster abstracts
Poster number 155 submitted by Michael Usewick
Functional Programmed -1 Ribosomal Frameshifting signals in the mRNA encoding human NSD1 may regulate histone methylation and transcription
Michael Usewick (First-year Innovation and Research Experience-FIRE University of Maryland), Lyra Morina (First-year Innovation and Research Experience-FIRE University of Maryland), Jerry Mi (First-year Innovation and Research Experience-FIRE University of Maryland), Vivek Advani (First-year Innovation and Research Experience-FIRE University of Maryland)
Abstract:
Recent studies have shown that Programmed -1 Ribosomal Frameshifting (-1 PRF) fits within the paradigm of post-transcription gene regulation (1,2,3). Characterization of numerous functional -1 PRF signals in the human genome suggests that it is a universal mechanism for regulating translation. It has also been shown that these -1 PRF signals function as mRNA destabilizing elements via nonsense mediated decay (NMD) (3,4). The observations that global dysregulation of -1 PRF has deleterious effects on gene expression leads us to hypothesize that ‘-1 PRF plays an important role in regulating cellular gene expression’. Bioinformatic analysis suggests 1,943 functional -1 PRF signals in the human genome (4,5). Through the First-year Innovative and Research Experiences (FIRE) - Found in Translation (FIT) Undergraduate Research Program at the University of Maryland College, we have identified functional -1 PRF signals encoded by over 40 human genes. Here, we have identified functional frameshift signals in mRNA encoding the nuclear receptor binding SET domain protein 1 (NSD1) gene. This gene encodes for histone methyltransferase that regulates chromosome arrangement and transcription. We hypothesize that the functional -1 PRF signal in NSD1 may contribute to regulating NSD1 expression and hence disease pathogenesis associated with NSD1. Dysregulation of NSD1 results in Sotos Syndrome, Acute myeloid leukemia, and Beckwith-Wiedemann Syndrome (6).
References:
1. Harger, J. et. al (2003). An in vivo dual-luciferase assay system for studying translational recoding in the yeast Saccharomyces cerevisiae. RNA, 1019-1024.
2.Dinman JD. Mechanisms and implications of programmed translational frameshifting. Wiley Interdiscip Rev RNA. 3(5):661-673. doi:10.1002/wrna.1126.
3.Belew, A. T. et. al (2011). Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast. Nucleic Acids Research, 39(7), 2799–808.
4.Belew, A. T. et. al (2008). PRFdb: a database of computationally predicted eukaryotic programmed -1 ribosomal frameshift signals. BMC Genomics, 9(1).
5.Belew, A. T., et. al (2014). Ribosomal frameshifting in the CCR5 mRNA is regulated by miRNAs and the NMD pathway. Nature, 512, 265–269.
6. NSD1 OMIM - http://www.omim.org/entry/606681
Keywords: -1 PRF, NSD1, Disease