Effect of ribosome shielding on mRNA stability

Based on the experimental evidence that translating ribosomes stabilize the mRNAs, we introduce and study a theoretical model for the dynamic shielding of mRNA by ribosomes. We present an improved fitting of published decay assay data in E. coli and show that only one third of the decay patterns are exponential. Our new transcriptome-wide estimate of the average lifetimes and mRNA half-lives shows that these timescales are considerably shorter than previous estimates. We also explain why there is a negative correlation between mRNA length and average lifetime when the mRNAs are subdivided in classes sharing the same degradation parameters. As a by-product, our model indicates that co-transcriptional translation in E. coli may be less common than previously believed.

[1]  R. Lipowsky,et al.  Length-dependent translation of messenger RNA by ribosomes. , 2011, Physical review. E, Statistical, nonlinear, and soft matter physics.

[2]  F. H. Schmidt,et al.  A computer program for modeling the kinetics of gene expression. , 1990, BioTechniques.

[3]  Gene-Wei Li,et al.  The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in bacteria , 2012, Nature.

[4]  C. Yanofsky,et al.  Polarity and the Degradation of mRNA , 1969, Nature.

[5]  C. Kurland,et al.  Codon usage determines translation rate in Escherichia coli. , 1989, Journal of molecular biology.

[6]  Anders F. Andersson,et al.  Global analysis of mRNA stability in the archaeon Sulfolobus , 2006, Genome Biology.

[7]  Arkady B. Khodursky,et al.  Global analysis of mRNA decay and abundance in Escherichia coli at single-gene resolution using two-color fluorescent DNA microarrays , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[8]  G. Stent.  Genetic transcription , 1966, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[9]  E. Marcotte,et al.  Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation , 2007, Nature Biotechnology.

[10]  H. M. Taylor,et al.  An introduction to stochastic modeling , 1985 .

[11]  Karen Willcox,et al.  Kinetics and kinematics for translational motions in microgravity during parabolic flight. , 2009, Aviation, space, and environmental medicine.

[12]  Isaac Meilijson,et al.  Genome-Scale Analysis of Translation Elongation with a Ribosome Flow Model , 2011, PLoS Comput. Biol..

[13]  R. Lipowsky,et al.  Complex Degradation Processes Lead to Non-Exponential Decay Patterns and Age-Dependent Decay Rates of Messenger RNA , 2013, PloS one.

[14]  M. Selbach,et al.  Global quantification of mammalian gene expression control , 2011, Nature.

[15]  P. Régnier,et al.  Ribosomes inhibit an RNase E cleavage which induces the decay of the rpsO mRNA of Escherichia coli , 1998, The EMBO journal.

[16]  D. Niu,et al.  Relationship Between mRNA Stability and Length: An Old Question with a New Twist , 2007, Biochemical Genetics.

[17]  Kim Sneppen,et al.  Ribosome collisions and translation efficiency: optimization by codon usage and mRNA destabilization. , 2008, Journal of molecular biology.

[18]  John D. Storey,et al.  Precision and functional specificity in mRNA decay , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Inhomogeneous exclusion processes and protein synthesis , 2006 .

[20]  R. Lipowsky,et al.  Translation by Ribosomes with mRNA Degradation: Exclusion Processes on Aging Tracks , 2011 .

[21]  Celso Grebogi,et al.  Queueing phase transition: theory of translation. , 2009, Physical review letters.

[22]  D. Gillespie.  A General Method for Numerically Simulating the Stochastic Time Evolution of Coupled Chemical Reactions , 1976 .

[23]  Ertugrul M. Ozbudak,et al.  Regulation of noise in the expression of a single gene , 2002, Nature Genetics.

[24]  A. Arkin,et al.  Stochastic mechanisms in gene expression. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[25]  E. Marcotte,et al.  Insights into the regulation of protein abundance from proteomic and transcriptomic analyses , 2012, Nature Reviews Genetics.

[26]  A. Valleriani,et al.  Transient Phenomena in Gene Expression after Induction of Transcription , 2012, PloS one.

[27]  S. Chisholm,et al.  Short RNA half-lives in the slow-growing marine cyanobacterium Prochlorococcus , 2010, Genome Biology.

[28]  Kim Sneppen,et al.  The functional half-life of an mRNA depends on the ribosome spacing in an early coding region. , 2011, Journal of molecular biology.

[29]  R K P Zia,et al.  Inhomogeneous exclusion processes with extended objects: the effect of defect locations. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[30]  R. Lipowsky,et al.  Turnover of messenger RNA: Polysome statistics beyond the steady state , 2010 .

[31]  Achim Tresch,et al.  Dynamic transcriptome analysis measures rates of mRNA synthesis and decay in yeast , 2011, Molecular systems biology.

[32]  John D. Storey,et al.  Genome-wide analysis of mRNA translation profiles in Saccharomyces cerevisiae , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[33]  F. H. Schmidt,et al.  The role of mRNA and protein stability in gene expression , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[34]  J. Belasco,et al.  Lost in translation: the influence of ribosomes on bacterial mRNA decay. , 2005, Genes & development.

[35]  Kelvin H. Lee,et al.  Totally asymmetric exclusion process with extended objects: a model for protein synthesis. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

[36]  Jaehun Lee,et al.  Hybrid system of semiconductor and photosynthetic protein , 2014, Nanotechnology.

[37]  J. Belasco.  All things must pass: contrasts and commonalities in eukaryotic and bacterial mRNA decay , 2010, Nature Reviews Molecular Cell Biology.

[38]  J. Belasco,et al.  Mechanisms of mRNA decay in bacteria: a perspective. , 1988, Gene.

[39]  G. Church,et al.  Global RNA half-life analysis in Escherichia coli reveals positional patterns of transcript degradation. , 2003, Genome research.

[40]  Nicholas T. Ingolia,et al.  Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes , 2011, Cell.

[41]  J. Weissman,et al.  Selective Ribosome Profiling Reveals the Cotranslational Chaperone Action of Trigger Factor In Vivo , 2011, Cell.