Ribosome profiling provides evidence that large non-coding RNAs do not encode proteins

By M. Guttman, Pamela Russell, Nicholas T. Ingolia, Jonathan S. Weissman, Eric S. Lander. Cell, 2013

732 citations recorded by the source corpus.

Summary Large non-coding 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, we show that classical non-coding 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 non-coding. Instead, we define a metric based on the known property of translation whereby translating ribosomes are released upon encountering a bona fide stop codon. We show that this metric accurately discriminates between protein-coding transcripts and all classes of known non-coding transcripts, including lincRNAs. Taken together, these results argue that the large majority of lincRNAs do not function through encoded proteins.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9216e95a349523c78f63a321e6c642b74059b5c5

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Citations in the corpus

Proteogenomics: concepts, applications, and computational strategies (2014, background): “The function and coding potential of transcripts annotated as lncRNAs is another very active area of research 75 .”
Ribosome profiling reveals pervasive translation outside of annotated protein-coding genes. (2014, background): “Whereas, based on both lack of conservation and the distribution of ribosome-protected fragments, there is strong evidence that most lncRNAs do not encode proteins with conserved adaptive cellular roles (Cabili et al., 2011; Chew et al., 2013; Guttman et al., 2013), these computational approaches co”
Detecting actively translated open reading frames in ribosome profiling data (2015, background): “Despite the identification of many PFPs in noncoding transcripts 10,11 , evolutionary-conservation analysis suggests that the act of translation, rather than the production of specific Articles peptides, may be the relevant process, which might explain the lack of matching peptides 31 .”
The Landscape of long non-coding RNA classification (2015, unknown): “Although many lncRNAs appear to associate with ribosomes [105, 114], this frequently does not result in protein synthesis [115, 116], but instead could reveal lncRNA regulation of translation [105].”
Diversity and dynamics of the Drosophila transcriptome (2014, unknown): “…of ribosome profiling initially indicated that a number of mammalian lncRNAs may be translated 43 , but this observation has been difficult to validate by proteomics 44 , and further analysis has suggested that although lncRNAs have signatures of ribosome occupancy, they are not translated 45 .”
LNCcation: lncRNA localization and function (2021, result): “, 2014) is not supported by other studies (Bánfai et al., 2012; Guttman et al., 2013).”
Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation (2014, methodology): “…recovered from ribosome profiling libraries always reflect a translating ribosome as opposed to regions protected by other RNA-binding proteins, or spurious binding to the ribosome (Guttman et al , 2013), and therefore, it is unclear how well these methods perform to identify individual smORFs.”
Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. (2016, background): “The criterion “non-coding” refers to the lack of open reading frames and/or conserved codons in transcripts, but remains controversial (8, 97, 118).”