Some lncRNAs associated with cancers. The colour represents either upregulated (red) or downregulated (blue) compared to normal tissues
Large-scale cDNA sequencing projects, together with technological advancements such as tiling arrays and the next generation RNA sequencing provided an unprecedented view of the transcriptome complexity. Surprisingly, only 1–2 % of the whole genome encodes proteins, with evidence of at least 80 % of the remainder being actively transcribed. These non-coding portions of the genome produce a large variety of mostly regulatory RNAs that differ in their biogenesis, properties and function, and are separated by their size into short, such as miRNAs and long (>200 nt) RNAs. The heterogeneous category of long non-coding RNAs (lncRNA) are especially abundant, accounting for 16,000 curated records in the current Gencode annotation (v.23) with for all lncRNA loci in the human genome numbering as high as 60,000.
lncRNAs remained elusive even in the genomics era due to their low expression levels and their presence in specific cell types, tissues or narrow time frames. They were identified as a class of RNA molecules in 2002, even though some lncRNA such as H19 and Xist were known since the early 1990s Analogous to protein coding genes but with low coding potential, these RNAs are usually transcribed by RNA polymerase II (Pol II), spliced, and mostly polyadenylated. Similarly, lncRNA promoters are enriched for active histone modifications typical of Pol II occupancy: H3K4me3, H3K9ac and H3K27ac. Even though the sequence of lncRNAs evolves rapidly, especially compared to their 3D structure, their tissue specificity as well as promotor sequences remain conserved as protein-coding genes. The heterogeneity of lncRNAs resonates in the diversity of their functions; lncRNAs interact with DNA, proteins and other RNAs to participate in processes from transcription, intracellular trafficking to chromosome remodelling as reviewed previously).
lncRNAs have been observed to regulate complex cellular behaviours such as growth, differentiation and establishment of cell identity that are commonly deregulated in cancer. Some have already been linked to poor prognosis in multiple tumour types and have a clinical relevance as biomarkers. (read more…)