Chew, G.L., Pauli, A., Rinn, J.L., Regev, A., Schier, A.F., and Valen, E. (2013) Ribosome profiling reveals resemblance between long non-coding RNAs and 5' leaders of coding RNAs. Development (Cambridge, England). 140(13):2828-2834.
Large-scale genomics and computational approaches have identified thousands of putative long non-coding RNAs (lncRNAs). It
has been controversial, however, as to what fraction of these RNAs is truly non-coding. Here, we combine ribosome profiling
with a machine-learning approach to validate lncRNAs during zebrafish development in a high throughput manner. We find that
dozens of proposed lncRNAs are protein-coding contaminants and that many lncRNAs have ribosome profiles that resemble the
52 leaders of coding RNAs. Analysis of ribosome profiling data from embryonic stem cells reveals similar properties for mammalian
lncRNAs. These results clarify the annotation of developmental lncRNAs and suggest a potential role for translation in lncRNA
regulation. In addition, our computational pipeline and ribosome profiling data provide a powerful resource for the identification
of translated open reading frames during zebrafish development.
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