Poster abstracts
Poster number 47 submitted by Mina Griffioen
Investigating regulation of eukaryotic gene expression by programmed -1 ribosomal frameshifting
Mina Griffioen (Cell biology and molecular genetics University of Maryland College Park), Liya Ket (Cell biology and molecular genetics University of Maryland College Park), Tania Mamdouhi (Cell biology and molecular genetics University of Maryland College Park), Arvin Massoudi (Cell biology and molecular genetics University of Maryland College Park), Vivek Advani (Cell biology and molecular genetics University of Maryland College Park), Jonathan D. Dinman (Cell biology and molecular genetics University of Maryland College Park)
Abstract:
Translational recoding refers to exception to the rules of translation. Programmed -1 ribosomal frameshifting (-1 PRF) is one such translational recoding mechanism first identified in some RNA viruses and later described in higher eukaryotes(1). A canonical ‘genomic’ -1 PRF signal directs an elongating ribosome to a -1 frame premature termination codon (PTC), thereby resulting in rapid degradation of the message through nonsense mediated mRNA decay (NMD) pathway. There exist an inverse relationship between -1 PRF efficiency and mRNA abundance(2). In silico analysis predicts that approximately 10% of genes in humans have at least one predicted -1 PRF signal(3). We have identified functional frameshift signals in mRNAs encoding human ATG7, EIF5B, BCL2L11, RASA2, and MAP4K3; as confirmed by bicistronic reporter assays. These are involved in translational initiation, apoptosis, cell stress, and cell signaling pathways. Additionally, preliminary data suggests that these -1PRF sequences function as mRNA destabilizing elements. Bioinformatic analysis suggests that microRNAs might be involved in regulating -1PRF efficiencies encoded by these messages.
References:
Jacobs JL, et. al. Identification of functional, endogenous programmed -1 ribosomal frameshift signals in the genome of Saccharomyces cerevisiae. NAR. 2007 Jan 12; 35(1):165–74.
2. Belew AT, et. al. Endogenous ribosomal frameshift signals operate as mRNA destabilizing elements through at least two molecular pathways in yeast. Nucleic Acids Res. 2011 Apr 1; 39(7):2799–808.
3. Belew AT, et. al. PRFdb: a database of computationally predicted eukaryotic programmed -1 ribosomal frameshift signals. BMC Genomics. 2008 Jan ;9(1):339.
Keywords: -1PRF, NMD, miRNA