Ribosome profiling: a Hi-Def monitor for protein synthesis at the genome-wide scale.
Bottom Line: Ribosome profiling of elongating ribosomes has been used for measuring differential gene expression at the level of translation, the identification of novel protein coding genes and ribosome pausing.It has also provided data for developing quantitative models of translation.Although only a dozen or so ribosome profiling datasets have been published so far, they have already dramatically changed our understanding of translational control and have led to new hypotheses regarding the origin of protein coding genes.
Affiliation: Biochemistry Department, University College Cork, Ireland.Show MeSH
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Mentions: Figure 3 illustrates why ribosome profiling of initiating ribosomes is particularly suitable for the detection of alternative protein isoforms (extensions and truncations of annotated CDS). As discussed in the section Ribosome Profiling of Initiating Ribosomes, initiation at alternative sites both upstream and downstream of the annotated protein coding ORFs is pervasive. Many of these events were heretofore difficult to detect and annotate. Now, advancements can be made in gene annotations by incorporating ribosome profiling data. Figure 10a shows an N-terminally extended isoform of the human RND3 gene which has an in-frame CUG initiating codon. Figure 10b shows a truncated isoform of the human CLK3 gene which Lee et al.12 found to initiate at an AUG codon downstream of the annotated AUG start codon. Ingolia et al.10 identified 570 genes with potential N-terminal extensions and 870 with N-terminal truncations in the 4994 genes that were analyzed in mESCs. Fritsch et al.13 also reported 546 N-terminal protein extensions in human (regions downstream of annotated starts were not analyzed). These examples highlight the usefulness of ribosome profiling data in improving existing annotations.
Affiliation: Biochemistry Department, University College Cork, Ireland.