Figure 2. Classification of ncRNA function.

a, Illustration of an ncRNA with expression patterns related to the NFκB pathway. Each row represents a gene, and a positive association (red box) is assigned between the ncRNA and the pathway based on the correlation of the genes in the process. Similarly, the ncRNA is assigned negative association (blue box) with the p53 pathway based on anticorrelation with the genes in the process. b, The scores for each functional term and ncRNA can be clustered to identify classes of ncRNAs. In this example (adapted, with permission, from ref. 25) each column represents a different ncRNA, and each row represents a different functional term. c, A model of ncRNAs that have a cis-function by remaining tethered to their site of transcription. In this model, RNA polymerase (green) transcribes an RNA (red), which can associate with regulatory proteins (purple) to affect neighbouring regions, as proposed for XIST^9,71. d, One model for ncRNA trans-regulation. In this model an ncRNA can associate with DNA-binding proteins (blue) and regulatory proteins to localize and affect the expression of the targets, as proposed for HOTAIR⁶⁴. e, A model for ncRNAs that bind regulatory proteins and change their activity, in this case leading to a change in modification state and expression of the target gene, as proposed for the CCND1 ncRNAs, which interact with the TLS protein⁸⁹. f, A model for ncRNAs that act as ‘decoys’. In this model, ncRNAs bind protein complexes and prevent them from binding to their proper regulatory targets, as proposed for GAS5 and PANDA²⁷.