Poster abstracts
Poster number 89 submitted by Sophie Martin
Codon optimality, translation elongation and the regulation of mRNA stability
Sophie Martin (Center for RNA Molecular Biology, CWRU), Ying-Hsin Chen (Center for RNA Molecular Biology, CWRU), Vladimir Presnyak (Center for RNA Molecular Biology, CWRU), Najwa Al Husaini (Center for RNA Molecular Biology, CWRU), Jeff Coller (Center for RNA Molecular Biology, CWRU)
Abstract:
A tight regulation of mRNA stability is essential in the control of gene expression. It has long been observed that mRNA decay and translation are intimately coupled, with mRNAs which translate being more stable. Translation efficiency depends on the supply of charged tRNAs in the cell and the demand by translating ribosomes (considering mRNA expression levels and the efficiency of tRNA interaction). Therefore, codons are considered “optimal” or “non-optimal” if the availability of cognate tRNAs exceeds or limits their relative usage. In the laboratory, it has been shown that the relative codon composition of an mRNA (optimal or non-optimal) directly influences mRNA stability, with mRNAs containing a high proportion of non-optimal codons being unstable. However, the mechanisms underlying the regulation of mRNA stability through codon decoding are unclear. Here, we sought to understand how translational elongation may be influenced by the codon composition of an mRNA and how this can lead to destabilization of the mRNA. First, we are investigating the relative occupancy of polyribosomes on highly “optimal” or “non-optimal” transcripts in yeast, to establish if mRNA stability is correlated with elongation rate. In conjunction, we are also studying how the decay of the stable PGK1 transcript can be affected by the introduction of synthetic non-optimal codons along the mRNA (different positions from 5’ to 3’), at which elongating ribosomes may be retained. Finally, we are analyzing the polysomal association of artificial optimal and non-optimal transcripts expressed in Drosophila melanogaster S2 cells, to determine if the codon optimality is a conserved determinant of gene expression in higher Eukaryotes. In particular, it is possible that codon composition is sensed during translation elongation, leading to repression of translation (and then decay, storage or transport). This would be a new aspect of gene expression possible differential regulation in distinct cell types, cellular environments or developmental states.
Keywords: mRNA decay, codon optimality, translation elongation