Fig. 2: Roles of long non-coding RNAs in nuclear organization.

a, 5′ small nucleolar RNA-capped and 3′-polyadenylated long non-coding (lncRNAs) (SPAs)⁴² and small nucleolar RNA-related lncRNAs (sno-lncRNAs)⁴¹ accumulate at their sites of transcription and interact with several splicing factors such as RNA-binding protein FOX-1 homologue 2 (RBFOX2), TAR DNA-binding protein 43 (TDP43) and heterogeneous nuclear ribonucleoprotein M (hnRNPM) to form a microscopically visible nuclear body that is involved in the regulation of alternative splicing⁴². b, The lncRNA functional intergenic repeating RNA element (Firre) is transcribed from the mouse X chromosome and interacts with the nuclear matrix factor hnRNPU to tether chromosome X (chrX), chr2, chr9, chr15 and chr17 into a nuclear domain^451,452. c, The lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is essential for the formation of paraspeckles¹⁷⁸. NEAT1 sequesters numerous paraspeckle proteins to form a highly organized core–shell (dark and light purple, respectively) spheroidal nuclear body⁴⁵³. The middle region of NEAT1 is localized in the centre of paraspeckles, and the 3′-end and 5′-end regions are localized in the periphery⁴⁵³. Different paraspeckle proteins are embedded by NEAT1 into the spheroidal structure in the core region (non-POU domain-containing octamer-binding protein (NONO), fused in sarcoma (FUS) and splicing factor, proline- and glutamine-rich (SFPQ)) or in the shell region (RNA-binding motif protein 14 (RBM14))⁴⁵³. d, The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is localized at the periphery of nuclear speckles^172,454 and is involved in the regulation of pre-mRNA splicing^339,455. MALAT1 interacts with the U1 small nuclear RNA (U1 snRNA)⁴²⁸, whereas proteins such as SON DNA- and RNA-binding protein and splicing component 35 kDa (SC35) are localized at the centre of nuclear speckles⁴⁵⁶. e, The lncRNA CHD2 adjacent, suppressive regulatory RNA (Chaserr) forms a compartment within a region of the mouse chromosome corresponding to a topologically associating domain that includes its own gene as well as the Chd2 gene (encoding chromodomain DNA helicase protein 2 (CHD2))⁴³⁷. Chaserr limits in cis the expression of Chd2, which is important for proper regulation of many genes (not shown). f, The perinucleolar compartment contains the lncRNA pyrimidine-rich non-coding transcript (PNCTR), which sequesters pyrimidine tract-binding protein 1 (PTBP1) and thus suppresses PTPBP1-mediated pre-mRNA splicing elsewhere in the nucleoplasm³⁶⁹. The size of nuclear bodies is indicated where relevant⁴⁵⁷. Figure adapted from ref. 80, Springer Nature. Part e courtesy of Inna-Marie Strazhnik and Mitch Guttman.