title: Cell cycle, oncogenic and tumor suppressor pathways regulate numerous long and macro non-protein-coding RNAs.
abstract: 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 non-coding 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 in the discovery of functionally relevant proteins and their deregulation is frequently associated with diseases. We therefore systematically identified lncRNAs expressed differentially in response to oncologically relevant processes and cell-cycle, p53 and STAT3 pathways, using tiling arrays.
  
  
  RESULTS
  We found that up to 80% of the pathway-triggered transcriptional responses are non-coding. Among these we identified very large macroRNAs with pathway-specific expression patterns and demonstrated 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.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hackermüller
authors.forename: Kristin
authors.initials: K
authors.lastname: Reiche
authors.forename: Christian
authors.initials: C
authors.lastname: Otto
authors.forename: Nadine
authors.initials: N
authors.lastname: Hösler
authors.forename: Conny
authors.initials: C
authors.lastname: Blumert
authors.forename: Katja
authors.initials: K
authors.lastname: Brocke-Heidrich
authors.forename: Levin
authors.initials: L
authors.lastname: Böhlig
authors.forename: Anne
authors.initials: A
authors.lastname: Nitsche
authors.forename: Katharina
authors.initials: K
authors.lastname: Kasack
authors.forename: Peter
authors.initials: P
authors.lastname: Ahnert
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Krupp
authors.forename: Kurt
authors.initials: K
authors.lastname: Engeland
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
authors.forename: Friedemann
authors.initials: F
authors.lastname: Horn
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; D015513:Oncogene Proteins; D062085:RNA, Long Noncoding; D025521:Tumor Suppressor Proteins