Fig. 3 ∣. Modular structures of long non-coding RNAs.

a, Targeted RNA sequencing has revealed that human chromosome 21 (chr21) is pervasively transcribed into long non-coding RNAs (lncRNAs) and that lncRNA exons are almost universally (but not randomly) alternatively spliced to form diverse and complex isoforms⁹⁸. The circle indicates the fraction of non-coding exons across all chr21 transcripts that are alternatively or constitutively spliced. b, Modular structural domains in lncRNAs that fulfil a range of functions^372-375, including targeting DNA, such as in the case of auxin-regulated promoter loop (APOLO)⁶¹; binding other RNAs – for example, terminal differentiation-induced non-coding RNA (TINCR)⁴⁵⁸, potentially involving RNA-binding proteins such as Staufen 1; and recruitment of proteins – for example, pyrimidine-rich non-coding transcript (PNCTR) recruiting of pyrimidine tract-binding protein 1 (PTBP1) through special RNA motifs³⁶⁹ and X-inactive-specific transcript (XIST) recruiting split ends homologue (SPEN) and Polycomb repressive complex 2 (PRC2), perhaps in concert, which is the subject of active exploration and debate^{142,397,399,423,424,459}. Modular functional domains can be repeated within a lncRNA or in multiple different lncRNAs^{7,87,186,369,388,391,393-401}. Figure courtesy of Tim R. Mercer.