Long Noncoding RNAs with Enhancer-like Function in Human Cells

Abstract

While the long non-coding RNAs (ncRNAs) constitute a large portion of the mammalian transcriptome, their biological functions has remained elusive. A few long ncRNAs that have been studied in any detail silence gene expression in processes such as X-inactivation and imprinting. We used a GENCODE annotation of the human genome to characterize over a thousand long ncRNAs that are expressed in multiple cell lines. Unexpectedly, we found an enhancer-like function for a set of these long ncRNAs in human cell lines. Depletion of a number of ncRNAs led to increased expression of their neighboring protein-coding genes, including the master regulator of hematopoiesis, SCL (also called TAL1), Snai1 and Snai2. Using heterologous transcription assays we demonstrated a requirement for the ncRNAs in mediating such enhancement of gene expression. These results reveal an unanticipated role for a class of long ncRNAs in activation of critical regulators of development and differentiation.

Mycobacteria modulate host epigenetic machinery by Rv1988 methylation of a non-tail arginine of histone H3

“…On the other hand, the association with H3 dimethyl arginine and repression was observed for TNFAIP2 and TRAF3, genes that are present almost 300-500 kb away from region B, indicating that the region within CDC42BPB probably was a regulatory element for TRAF3 and TNFAIP2. Moreover, the finding that the expression of lincRNA ENSG00000250584 was also altered fits well with the known regulatory role of lincRNAs 40 .…”

Aberrant expression of long noncoding RNAs in cumulus cells isolated from PCOS patients

“…Each array contains probes that interrogate approximately 39,000 human lncRNAs and approximately 32,000 mRNAs. These lncRNA and mRNA target sequences were merged from multiple authoritative databases: 4765 from RefSeq, 12,754 from ENSEMBL, 8195 lincRNA from John Rinn's lab [30], 1289 from NRED (ncRNA Expression Database), 17,203 from HInvDB, 2975 from ENCODE, 529 from CombinedLit, 1053 from Antisense ncRNA pipeline, 407 Hox ncRNAs, 481 UCRs, and 848 from Chen Ruisheng's laboratory (Institute of Biophysics, Chinese Academy of Science). The array also contains 4974 Agilent control probes.…”

“…To further understand the features of differentially expressed lncRNAs isolated in this study, we classified the lncRNAs as follows: lncRNAs with enhancer-like functions, Rinn's lincRNAs, and HOX cluster lncRNAs. Of these classes, lncRNAs with enhancer-like functions were identified using the GENCODE annotation of human genes [30,32]; transcripts mapped to the exons and introns of annotated protein-coding genes, natural antisense transcripts that overlap the protein-coding genes and all known transcripts were excluded. Rinn's lincRNA and HOX cluster lncRNAs were identified according to Rinn's reports [33][34][35].…”

Identification and Characterization of a Noncoding RNA at the Mouse Pcna Locus

“…Although genetic or epigenetic differences between normal and cancer cells might cause a different susceptibility to RNAi, the results in cancerous cells (B16F10, B16BL6 and LLC) was different, still suggesting that a regulatory system mediated by ncRNA is somehow disrupted in cancer cells (Fig. 4) Although the precise mechanism by which AK007836 activates neighboring coding gene expression is still unknown, it might be an example of a class of long ncRNAs having a positive effect on gene expression (Feng et al, 2006;Lanz et al, 1999;Ørom et al, 2010;Shamovsky et al, 2006). Accumulating evidence indicate that a variety of promoter associated ncRNAs such as promoter-associated long RNAs (PALRs), promoter-associated short RNAs (PASRs), and promoter upstream transcripts (PROMTs), etc., are involved in the protein coding gene transcription (suppression or activation) through epigenetic modification in addition to transcriptional interferences (Carninci, 2010;Costa, 2010;Han et al, 2007;Morris et al, 2008;Preker et al, 2008).…”