Researchers from the Case Western Reserve School of Medicine say they have not only identified thousands of novel long noncoding ribonucleic acid (lncRNA) transcripts but also discovered that, contrary to popular belief, some of them actually do direct the synthesis of proteins in cells. They published their study (“Translation of Small Open Reading Frames within Unannotated RNA Transcripts in Saccharomyces cerevisiae”) in Cell Reports.

Kristian E. Baker, Ph.D., assistant professor in the Center for RNA Molecular Biology, led the team that applied high-throughput gene expression analysis to yield these findings, which, the scientist noted, ultimately could lead to treatments for cancer and some genetic disorders. “Our work establishes that lncRNAs in yeast can encode proteins, and we provide evidence that this is probably true also in mammals, including humans,” Dr. Baker said. “Our investigation has expanded our knowledge of the genetic coding potential of already well-characterized genomes.”

Collaborating with researchers including Case Western Reserve University graduate and undergraduate students, Dr. Baker analyzed yeast and mouse cells, which serve as model organisms because of their functional resemblance to human cells.

Previously, lncRNAs were thought to lack the information and capacity to encode for proteins, distinguishing them from the messenger RNAs that are expressed from known genes and act primarily as templates for the synthesis of proteins. Yet this team demonstrated that a subset of these lncRNAs is engaged by the translation machinery and can function to produce protein products.

“We validate expression of peptides encoded within a subset of these RNAs and provide evidence for conservation among yeast species. Consistent with their translation, many of these transcripts are targeted for degradation by the translation-dependent nonsense-mediated RNA decay (NMD) pathway,” wrote the investigators. “We identify lncRNAs that are also sensitive to NMD, indicating that translation of noncoding transcripts also occurs in mammals. These data demonstrate transcripts considered to lack coding potential are bona fide protein coding and expand the proteome of yeast and possibly other eukaryotes.”

In the future, Dr. Baker and fellow investigators will continue to look for novel RNA transcripts and also search for a function for these lncRNAs and their protein products in cells.

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