Poster abstracts

Poster number 6 submitted by James Aretakis

Exploring the global determinants of bacterial mRNA decay

James R. Aretakis (Wayne State University, Department of Biological Sciences, Detroit, MI 48202), Nadra Al-Husini (Wayne State University, Department of Biological Sciences, Detroit, MI 48202), Mohammed-Husain M. Bharmal (Wayne State University, Department of Biological Sciences, Detroit, MI 48202), Nisansala S. Muthunayake (Wayne State University, Department of Biological Sciences, Detroit, MI 48202), Jared M. Schrader (Wayne State University, Department of Biological Sciences, Detroit, MI 48202)

Abstract:
In eukaryotes global mRNA half-lives are strongly influenced by translation elongation1 and by the rate of translation initiation2. In bacteria it is unclear what mRNA features influence global mRNA half-lives. In addition, phase-separated BR-bodies, analogous to eukaryotic P-bodies, contribute to mRNA degradation by stimulating the rate of mRNA decay3,4. Here we measure the genome-wide mRNA decay rates in Caulobacter crescentus. Then using this mRNA dataset, we investigate what features control mRNA degradation in bacteria. The strongest correlation (R=0.49) we found with mRNA half-life is codon usage, suggesting translation elongation is a dominant factor. Translation efficiency provides the next strongest correlation (R=0.30), and GC content (R=-0.18) and mRNA length (R=-0.06), which are associated with BR-body enrichment, are inversely correlated. As translation efficiency is a measure of both translation initiation and translation elongation, we are using synthetic mRNAs to separate and vary these two translation phases independently to determine which mRNA translation phase has the largest influence on mRNA degradation. Furthermore, we will follow up by probing the mechanisms by which translating ribosomes can either stabilize or destabilize mRNAs. Ultimately, this information will allow us to compare how mRNA decay is controlled between eukaryotic and bacterial cells.

References:
1Presnyak, Vladimir, et al. "Codon optimality is a major determinant of mRNA stability." Cell 160.6 (2015): 1111-1124.

2Chan, Leon Y., et al. "Non-invasive measurement of mRNA decay reveals translation initiation as the major determinant of mRNA stability." eLIFE 7 (2018): e32536.

3Al-Husini, Nadra, et al. "α-Proteobacterial RNA Degradosomes Assemble Liquid-Liquid Phase-Separated RNP Bodies." Molecular cell 71.6 (2018): 1027-1039.

4Al-Husini, Nadra, et al. "BR-bodies provide selectively permeable condensates that stimulate mRNA decay and prevent release of decay intermediates." bioRxiv (2019): 690628.

Keywords: mRNA Decay, translation elongation, translation initiation