Poster Presentation 40th Annual Lorne Genome Conference 2019

Evolutionary sequence conservation reveals the majority of human long non-coding RNAs are likely non-functional (#227)

Walter Muskovic 1 , Maria Kavallaris 1
  1. Children's Cancer Institute, Australia, Kirribilli, NSW, Australia

Pervasive transcription throughout the human genome gives rise to tens of thousands of long non-coding RNA (lncRNA) transcripts. Despite extensive efforts, the functional significance of the vast majority of these transcripts remains undetermined. Evolutionary sequence conservation has proven a powerful method to identify functional sequence elements in the human genome. We defined signatures of sequence conservation consistent with the sequence-, structure- and transcription-dependent roles that experimentally characterised lncRNAs are reported to maintain. We report that the majority of lncRNA exon sequences are not conserved. Polyadenylation signal and core promoter motifs associated with the initiation of transcription are similarly not evolutionarily conserved. The widely reported conservation of lncRNA promoter regions is revealed to be upstream of core promoter motifs, consistent with predictions that lncRNAs are by-products of transcription associated with active enhancers. The results of this study suggest the cell-type specificity characteristic of lncRNAs is a reflection of the specificity of active enhancer elements and the majority of lncRNAs transcripts are themselves likely non-functional.