The long non-coding RNA Dali is an epigenetic regulator of neural differentiation

Abstract

Many intergenic long noncoding RNA (lncRNA) loci regulate the expression of adjacent protein coding genes. Less clear is whether intergenic lncRNAs commonly regulate transcription by modulating chromatin at genomically distant loci. Here, we report both genomically local and distal RNA-dependent roles of Dali, a conserved central nervous system expressed intergenic lncRNA. Dali is transcribed downstream of the Pou3f3 transcription factor gene and its depletion disrupts the differentiation of neuroblastoma cells. Locally, Dali transcript regulates transcription of the Pou3f3 locus. Distally, it preferentially targets active promoters and regulates expression of neural differentiation genes, in part through physical association with the POU3F3 protein. Dali interacts with the DNMT1 DNA methyltransferase in mouse and human and regulates DNA methylation status of CpG island-associated promoters in trans. These results demonstrate, for the first time, that a single intergenic lncRNA controls the activity and methylation of genomically distal regulatory elements to modulate large-scale transcriptional programmes.DOI: http://dx.doi.org/10.7554/eLife.04530.001

Linking RNA biology to lncRNAs

“…One of the biggest concerns with any RNAi or RNase H-mediated depletion of lncRNAs is the significant differences in abundance that exist between mRNAs and lncRNAs; even if the most judicious controls are used (Jackson et al 2003;Adamson et al 2012;Sigoillot et al 2012). For example, the lncRNA DALIR was recently detected at two molecules per cell (Chalei et al 2014), and shRNA-mediated depletion of this RNA molecule resulted in the significant differential regulation of more than 200 genes in N2A cells. Given the low abundance of DALIR transcripts in this context and the excess of targeting shRNA molecules, the likelihood of off-target affects rises by orders of magnitude as has been previously suggested (Bassett et al 2014).…”

A DNS-metiláció szerepe és megváltozása az öregedés és a daganatos betegségek kialakulása során

“…Az ecCEBP lncRNS például a DNMT1 enzimhez kötődve specifikusan a CEBPA locus promóterének metilációját szabályozza [53]. További példák közé tartozik a központi idegrendszer Dali nevű lncRNS-e, amely szintén a DNMT1-gyel alkot komplexet [54]. A lncRNS-ek e metilációt irányító funkciója mellett ismert olyan példa is, ami esetén a lncRNS expressziója szabályozott DNS-metiláció által [55].…”

HOXA-AS2 Promotes Proliferation and Induces Epithelial-Mesenchymal Transition via the miR-520c-3p/GPC3 Axis in Hepatocellular Carcinoma

“…Recent studies showed that lncRNA can act as oncogenes or tumor suppressors in malignant tumors, suggesting that the aberrant expression of lncRNAs is associated with tumorigenesis of many types of cancers [7,8]. Abnormal lncRNA expression and its association with various important clinicopathological parameters have been reported in HCC [9,10].…”