Ribosome Profiling Provides Evidence that Large Noncoding RNAs Do Not Encode Proteins

Large noncoding RNAs are emerging as an important component in cellular regulation. Considerable evidence indicates that these transcripts act directly as functional RNAs rather than through an encoded protein product. However, a recent study of ribosome occupancy reported that many large intergenic ncRNAs (lincRNAs) are bound by ribosomes, raising the possibility that they are translated into proteins.

Here, researchers from the Broad Institute of MIT and Harvard show that classical noncoding RNAs and 5′ UTRs show the same ribosome occupancy as lincRNAs, demonstrating that ribosome occupancy alone is not sufficient to classify transcripts as coding or noncoding. Instead, they  define a metric based on the known property of translation whereby translating ribosomes are released upon encountering a bona fide stop codon. They show that this metric accurately discriminates between protein-coding transcripts and all classes of known noncoding transcripts, including lincRNAs. Taken together, these results argue that the large majority of lincRNAs do not function through encoded proteins.

• Guttman M, Russell P, Ingolia NT, Weissman JS, Lander ES. (2013) Ribosome Profiling Provides Evidence that Large Noncoding RNAs Do Not Encode Proteins. Cell  154(1), 240-51. [abstract]