Cell cycle, oncogenic and tumor suppressor pathways regulate numerous long and macro non-protein coding RNAs
Menée sur des lignées cellulaires, cette étude identifie un ensemble de voies de signalisation liées à des oncogènes ou suppresseurs de tumeurs et impliquées dans la régulation de l'expression de longs ARNs non codants
BACKGROUND:The genome is pervasively transcribed but most transcripts do not code for proteins, constituting non-protein coding RNAs. Despite increasing numbers of functional reports of individual long noncoding RNAs (lncRNAs), assessing the extent of functionality among the non-coding transcriptional output of mammalian cells remains intricate. In the protein coding world, transcripts differentially expressed in the context of processes essential for the survival of multicellular organisms have been instrumental for the discovery of functionally relevant proteins and their deregulation is frequently associated with diseases. We therefore systematically identify lncRNAs expressed differentially in response to oncologically relevant processes, cell-cycle, p53-, and STAT3 pathway, using tiling arrays. RESULTS:We find that up to 80% of the pathway-triggered transcriptional response can be non-coding. Among these we identify very large macroRNAs with pathway-specific expression patterns and demonstrate that these are likely continuous transcripts. MacroRNAs contain elements conserved in mammals and sauropsids, which in part exhibit conserved RNA secondary structure. Comparing evolutionary rates of a macroRNA to adjacent protein coding genes suggests a local action of the transcript. Finally, in different grades of astrocytoma, a tumor disease unrelated to the initially used cell lines, macroRNAs are differentially expressed. CONCLUSIONS:It has been shown previously that the majority of expressed non-ribosomal transcripts are non-coding. We now conclude that differential expression triggered by signaling pathways gives rise to a similar abundance of non-coding content. It is thus unlikely that the prevalence of non-coding transcripts in the cell is a trivial consequence of leaky or random transcription events.