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Causal signals between codon bias, mRNA structure, and the efficiency of translation and elongation.

Pop C, Rouskin S, Ingolia NT, Han L, Phizicky EM, Weissman JS, Koller D - Mol. Syst. Biol. (2014)

Bottom Line: We present a robust method to extract codon translation rates and protein synthesis rates from these data, and identify causal features associated with elongation and translation efficiency in physiological conditions in yeast.Deletion of three of the four copies of the heavily used ACA tRNA shows a modest efficiency decrease that could be explained by other rate-reducing signals at gene start.We also show a correlation between efficiency and RNA structure calculated both computationally and from recent structure probing data, as well as the Kozak initiation motif, which may comprise a mechanism to regulate initiation.

View Article: PubMed Central - PubMed

Affiliation: Computer Science Department, Stanford University, Stanford, CA, USA cpop@cs.stanford.edu.

No MeSH data available.


RNA structure energy and its relationship to translation efficiencyLeft: Energy averaged in sliding windows of 40 nt (see Materials and Methods) across all genes for in vitro and in vivo measures of energy via DMS probing (Rouskin et al, 2013). The second red line corresponds to the first window with lowest energy (˜60 nt for in vitro and ˜80 nt in vivo).Right: Spearman correlation between the energy windows and TE. The first red line corresponds to the first window with significant correlation (9 nt for in vitro and 18 nt for in vivo).
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fig06: RNA structure energy and its relationship to translation efficiencyLeft: Energy averaged in sliding windows of 40 nt (see Materials and Methods) across all genes for in vitro and in vivo measures of energy via DMS probing (Rouskin et al, 2013). The second red line corresponds to the first window with lowest energy (˜60 nt for in vitro and ˜80 nt in vivo).Right: Spearman correlation between the energy windows and TE. The first red line corresponds to the first window with significant correlation (9 nt for in vitro and 18 nt for in vivo).

Mentions: Structure is reduced near the translation start site in many organisms (Gu et al, 2010; Zhou & Wilke, 2011) and, in combination with specific structural motifs downstream, can promote or halt initiation (Kozak, 1990; Kochetov et al, 2007; Robbins-Pianka et al, 2010). We performed a sliding window analysis (see Materials and Methods and Fig6) to correlate TE with RNA secondary structure in 40 nt windows along the gene, for both experimental in vitro and in vivo structural energy (Rouskin et al, 2013). The window near the start codon is most significant, as reported previously for computational and in vitro structure measurements (Kudla et al, 2009; Kertesz et al, 2010; Tuller et al, 2010b; Keller et al, 2012); the positive correlation indicates that increased TE corresponds to loose structure in this region. Indeed, this is also the window with highest energy, corresponding to the lowest structure, as averaged over all genes (first red line in Fig6). Interestingly, the correlation with TE for in vivo structure is less pronounced and the window is shifted 3 codons downstream. We call this Window A.


Causal signals between codon bias, mRNA structure, and the efficiency of translation and elongation.

Pop C, Rouskin S, Ingolia NT, Han L, Phizicky EM, Weissman JS, Koller D - Mol. Syst. Biol. (2014)

RNA structure energy and its relationship to translation efficiencyLeft: Energy averaged in sliding windows of 40 nt (see Materials and Methods) across all genes for in vitro and in vivo measures of energy via DMS probing (Rouskin et al, 2013). The second red line corresponds to the first window with lowest energy (˜60 nt for in vitro and ˜80 nt in vivo).Right: Spearman correlation between the energy windows and TE. The first red line corresponds to the first window with significant correlation (9 nt for in vitro and 18 nt for in vivo).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4300493&req=5

fig06: RNA structure energy and its relationship to translation efficiencyLeft: Energy averaged in sliding windows of 40 nt (see Materials and Methods) across all genes for in vitro and in vivo measures of energy via DMS probing (Rouskin et al, 2013). The second red line corresponds to the first window with lowest energy (˜60 nt for in vitro and ˜80 nt in vivo).Right: Spearman correlation between the energy windows and TE. The first red line corresponds to the first window with significant correlation (9 nt for in vitro and 18 nt for in vivo).
Mentions: Structure is reduced near the translation start site in many organisms (Gu et al, 2010; Zhou & Wilke, 2011) and, in combination with specific structural motifs downstream, can promote or halt initiation (Kozak, 1990; Kochetov et al, 2007; Robbins-Pianka et al, 2010). We performed a sliding window analysis (see Materials and Methods and Fig6) to correlate TE with RNA secondary structure in 40 nt windows along the gene, for both experimental in vitro and in vivo structural energy (Rouskin et al, 2013). The window near the start codon is most significant, as reported previously for computational and in vitro structure measurements (Kudla et al, 2009; Kertesz et al, 2010; Tuller et al, 2010b; Keller et al, 2012); the positive correlation indicates that increased TE corresponds to loose structure in this region. Indeed, this is also the window with highest energy, corresponding to the lowest structure, as averaged over all genes (first red line in Fig6). Interestingly, the correlation with TE for in vivo structure is less pronounced and the window is shifted 3 codons downstream. We call this Window A.

Bottom Line: We present a robust method to extract codon translation rates and protein synthesis rates from these data, and identify causal features associated with elongation and translation efficiency in physiological conditions in yeast.Deletion of three of the four copies of the heavily used ACA tRNA shows a modest efficiency decrease that could be explained by other rate-reducing signals at gene start.We also show a correlation between efficiency and RNA structure calculated both computationally and from recent structure probing data, as well as the Kozak initiation motif, which may comprise a mechanism to regulate initiation.

View Article: PubMed Central - PubMed

Affiliation: Computer Science Department, Stanford University, Stanford, CA, USA cpop@cs.stanford.edu.

No MeSH data available.