Measurement of average decoding rates of the 61 sense codons in vivo.
Measurement of average decoding rates of the 61 sense codons in vivo.
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DOI：
10.7554/elife.03735
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发表时间：
2014-10-27
期刊：
影响因子：
7.7
通讯作者：
Futcher B
中科院分区：
文献类型：
--
作者：
Gardin J;Yeasmin R;Yurovsky A;Cai Y;Skiena S;Futcher B
Most amino acids can be encoded by several synonymous codons, which are used at unequal frequencies. The significance of unequal codon usage remains unclear. One hypothesis is that frequent codons are translated relatively rapidly. However, there is little direct, in vivo, evidence regarding codon-specific translation rates. In this study, we generate high-coverage data using ribosome profiling in yeast, analyze using a novel algorithm, and deduce events at the A- and P-sites of the ribosome. Different codons are decoded at different rates in the A-site. In general, frequent codons are decoded more quickly than rare codons, and AT-rich codons are decoded more quickly than GC-rich codons. At the P-site, proline is slow in forming peptide bonds. We also apply our algorithm to short footprints from a different conformation of the ribosome and find strong amino acid-specific (not codon-specific) effects that may reflect interactions with the exit tunnel of the ribosome. DOI: http://dx.doi.org/10.7554/eLife.03735.001 Genes contain the instructions for making proteins from molecules called amino acids. These instructions are encoded in the order of the four building blocks that make up DNA, which are symbolized by the letters A, T, C, and G. The DNA of a gene is first copied to make a molecule of RNA, and then the letters in the RNA are read in groups of three (called ‘codons’) by a cellular machine called a ribosome. ‘Sense codons’ each specify one amino acid, and the ribosome decodes hundreds or thousands of these codons into a chain of amino acids to form a protein. ‘Stop codons’ do not encode amino acids but instead instruct the ribosome to stop building a protein when the chain is completed. Most proteins are built from 20 different kinds of amino acid, but there are 61 sense codons. As such, up to six codons can code for the same amino acid. The multiple codons for a single amino acid, however, are not used equally in gene sequences—some are used much more often than others. Now, Gardin, Yeasmin et al. have instantly halted the on-going processes of decoding genes and building proteins in yeast cells. Codons being translated into amino acids are trapped inside the ribosome; and codons that take the longest to decode are trapped most often. By using a computer algorithm, Gardin, Yeasmin et al. were able to measure just how often each kind of sense codon was trapped inside the ribosome and use this as a measure of how quickly each codon is decoded. The more often a given codon is used in a gene sequence, the less likely it was found to be trapped inside the ribosome—which suggests that these codons are decoded quicker than other codons and pass through the ribosome more quickly. Put another way, it appears that genes tend to use the codons that can be read the fastest. Certain properties of a codon also affected its decoding speed. Codons with more As and Ts, for example, are decoded faster than codons with more Cs and Gs. Furthermore, whenever a chemically unusual amino acid called proline has to be added to a new protein chain, it slowed down the speed at which the protein was built. The method described by Gardin, Yeasmin et al. for peering into a decoding ribosome may now help future studies that aim to answer other questions about how proteins are built. DOI: http://dx.doi.org/10.7554/eLife.03735.002
