An intragenic long noncoding RNA interacts epigenetically with the RUNX1 promoter and enhancer chromatin DNA in hematopoietic malignancies

RUNX1, a master regulator of hematopoiesis, is the most commonly perturbed target of chromosomal abnormalities in hematopoietic malignancies. The t(8;21) More »

Role of the lncRNA-p53 regulatory network in cancer

Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs (lncRNAs). Emerging More »

Everything old is new again: (linc)RNAs make proteins!

Conventional protein-coding genes account for only a fraction of the RNA transcribed in animal genomes. Many of us grew up More »

Some long non-coding RNAs are conventional after all

from ScienceDaily Not so long ago researchers thought that RNAs came in two types: coding RNAs that make proteins and More »

The Circulating Long Non-Coding RNA LIPCAR Predicts Survival in Heart Failure Patients

Long non-coding RNAs (lncRNAs) represent a novel class of molecules regulating gene expression. LncRNAs are present in body fluids, but More »

 

A Network Based Method for Analysis of lncRNA-Disease Associations and Prediction of lncRNAs Implicated in Diseases

Increasing evidence has indicated that long non-coding RNAs (lncRNAs) are implicated in and associated with many complex human diseases. Despite of the accumulation of lncRNA-disease associations, only a few studies had studied the roles of these associations in pathogenesis.

In this paper, researchers at Xidian University investigated lncRNA-disease associations from a network view to understand the contribution of these lncRNAs to complex diseases. Specifically, they studied both the properties of the diseases in which the lncRNAs were implicated, and that of the lncRNAs associated with complex diseases. Regarding the fact that protein coding genes and lncRNAs are involved in human diseases, they constructed a coding-non-coding gene-disease bipartite network based on known associations between diseases and disease-causing genes. The researchers then applied a propagation algorithm to uncover the hidden lncRNA-disease associations in this network. The algorithm was evaluated by leave-one-out cross validation on 103 diseases in which at least two genes were known to be involved, and achieved an AUC of 0.7881. This algorithm successfully predicted 768 potential lncRNA-disease associations between 66 lncRNAs and 193 diseases. Furthermore, their results for Alzheimer’s disease, pancreatic cancer, and gastric cancer were verified by other independent studies.

lncRNA

  • Yang X, Gao L, Guo X, Shi X, Wu H, et al. (2014) A Network Based Method for Analysis of lncRNA-Disease Associations and Prediction of lncRNAs Implicated in Diseases. PLoS ONE 9(1),  e87797. [article]

An intragenic long noncoding RNA interacts epigenetically with the RUNX1 promoter and enhancer chromatin DNA in hematopoietic malignancies

lncRNA

RUNX1, a master regulator of hematopoiesis, is the most commonly perturbed target of chromosomal abnormalities in hematopoietic malignancies. The t(8;21) translocation is found in 30%-40% of cases of acute myeloid leukemia (AML). Recent whole-exome sequencing also reveals mutations and deletions of RUNX1 in some solid tumors.

Researchers from Jilin University, China describe a RUNX1-intragenic long noncoding RNA ROPNR that is transcribed as unspliced transcript from an upstream overlapping promoter. ROPNR was upregulated in AML samples and in response to Ara-C treatment in vitro. ROPNR utilizes its 3′-terminal fragment to directly interact with the RUNX1 promoter and enhancers and participates in the orchestration of an intrachromosomal loop. The 3′ region of ROPNR also participates in long-range interchromosomal interactions with chromatin regions that are involved in multiple RUNX1 translocations. These data suggest that ROPNR noncoding RNA may function as a previously unidentified candidate component that is involved in chromosomal translocation in hematopoietic malignancies.

  • Wang H, Li W, Guo R, Sun J, Cui J, Wang G, Hoffman AR, Hu JF. (2014) An intragenic long noncoding RNA interacts epigenetically with the RUNX1 promoter and enhancer chromatin DNA in hematopoietic malignancies. Int J Cancer [Epub ahead of print]. [abstract]

Species-specific alternative splicing leads to unique expression of sno-lncRNAs

Intron-derived long noncoding RNAs with snoRNA ends (sno-lncRNAs) are highly expressed from the imprinted Prader-Willi syndrome (PWS) region on human chromosome 15. However, sno-lncRNAs from other regions of the human genome or from other genomes have not yet been documented.

By exploring non-polyadenylated transcriptomes from human, rhesus and mouse, researchers at the Shanghai Institutes for Biological Sciences have systematically annotated sno-lncRNAs expressed in all three species. In total, using available data from a limited set of cell lines, 19 sno-lncRNAs have been identified with tissue- and species-specific expression patterns. Although primary sequence analysis revealed that snoRNAs themselves are conserved from human to mouse, sno-lncRNAs are not. PWS region sno-lncRNAs are highly expressed in human and rhesus monkey, but are undetectable in mouse. Importantly, the absence of PWS region sno-lncRNAs in mouse suggested a possible reason why current mouse models fail to fully recapitulate pathological features of human PWS. In addition, a RPL13A region sno-lncRNA was specifically revealed in mouse embryonic stem cells, and its snoRNA ends were reported to influence lipid metabolism. Interestingly, the RPL13A region sno-lncRNA is barely detectable in human. The researchers further demonstrated that the formation of sno-lncRNAs is often associated with alternative splicing of exons within their parent genes, and species-specific alternative splicing leads to unique expression pattern of sno-lncRNAs in different animals.

lncRNA

Comparative transcriptomes of non-polyadenylated RNAs among human, rhesus and mouse revealed that the expression of sno-lncRNAs is species-specific and that their processing is closely linked to alternative splicing of their parent genes. This study thus further demonstrates a complex regulatory network of coding and noncoding parts of the mammalian genome.

  • Zhang XO, Yin QF, Wang HB, Zhang Y, Chen T, Zheng P, Lu X, Chen LL, Yang L. (2014) Species-specific alternative splicing leads to unique expression of sno-lncRNAs. BMC Genomics 15(1), 287. [abstract]

Role of the lncRNA-p53 regulatory network in cancer

lncRNA

Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs (lncRNAs). Emerging evidence indicates that lncRNAs may serve as master gene regulators through various mechanisms. Dysregulation of lncRNAs is often associated with a variety of human diseases including cancer. Of significant interest, recent studies suggest that lncRNAs participate in the p53 tumor suppressor regulatory network. In this review, the authors discuss how lncRNAs serve as p53 regulators or p53 effectors. Further characterization of these p53-associated lncRNAs in cancer will provide a better understanding of lncRNA-mediated gene regulation in the p53 pathway. As a result, lncRNAs may prove to be valuable biomarkers for cancer diagnosis or potential targets for cancer therapy.

  • Zhang A, Xu M, Mo YY. (2014) Role of the lncRNA-p53 regulatory network in cancer. J Mol Cell Biol [Epub ahead of print]. [article]

Everything old is new again: (linc)RNAs make proteins!

lncRNA

Conventional protein-coding genes account for only a fraction of the RNA transcribed in animal genomes. Many of us grew up thinking that RNAs came in two flavours: those with protein-coding capacity and non-coding RNAs with structural roles, in the form of ribosomal RNAs, tRNAs, snoRNAs, etc. Interest in other forms of long non-coding RNAs (lincRNAs) has been growing over the past decade, building in part on the fact that many lincRNAs are the precursors for micro-RNA biogenesis. In some cases, the miRNA is the only known product of a primary transcript that can be tens of Kb in length. But there is much more to lincRNAs: functions include X inactivation and other forms of chromatin modification (Gupta et al, 2010; Tian et al, 2010), enhancer-like functions regulating transcription (Orom et al, 2010) and regulation of post-transcriptional gene expression by functioning as micro-RNA sponges (Hansen et al, 2013; Memczak et al, 2013). Recent papers from the Couso, Schier and Giraldez/Rajewsky laboratories now bring us full circle, assigning a protein-coding function to lincRNAs  (Magny et al, 2013; Pauli et al, 2014), (Bazzini et al, 2014).

  • Cohen SM. (2014) Everything old is new again: (linc)RNAs make proteins! EMBO J [Epub ahead of print]. [abstract]