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 »

Featured long non-coding RNA – PCAT-1

Impairment of double-stranded DNA break (DSB) repair is essential to many cancers. However, although mutations in DSB repair proteins are More »

Featured long non-coding RNA: CARLo-5

The mechanism by which the 8q24 MYC enhancer region, including cancer-associated variant rs6983267, increases cancer risk is unknown due to More »

 

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]

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, we 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. Researchers at the Shanghai Institutes for Biological Sciences 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]

Featured long non-coding RNA – SENCR

There is little insight into whether and how lncRNAs effect human vascular cell phenotypes.  Now, researchers at the University of Rochester School of Medicine and Dentistry have performed RNA sequencing in human coronary artery smooth muscle cells and discovered a novel lncRNA called SENCR.  SENCR is most abundant in vascular smooth muscle cells and endothelial cells.  SENCR is a low copy, cytoplasmic lncRNA whose knockdown results in reduced expression of vascular smooth muscle contractile genes.  On the other hand, many migratory genes are elevated upon SENCR knockdown.  Accordingly, human smooth muscle cells with reduced SENCR show hypermotility in vitro, a phenotype that is completely rescued with simultaneous knockdown of either of two pro-migratory genes (MDK, PTN).  Consistent with its cytoplasmic localization, knockdown of SENCR has little cis-acting effect on  neighboring gene expression.  SENCR is one of the first 5′ overlapping antisense lncRNAs to be studied in detail.

lncRNA

  • Bell RD, Long X, Lin M, Bergmann JH, Nanda V, Cowan SL, Zhou Q, Han Y, Spector DL, Zheng D, Miano JM. (2014) Identification and Initial Functional Characterization of a Human Vascular Cell-Enriched Long Noncoding RNA. Arterioscler Thromb Vasc Biol [Epub ahead of print]. [abstract]

A short guide to long non-coding RNA gene nomenclature

The HUGO Gene Nomenclature Committee (HGNC) is the only organisation authorised to assign standardised nomenclature to human genes. Of the 38,000 approved gene symbols in the database (www.genenames.org), the majority represent protein-coding (pc) genes; however, also named are pseudogenes, phenotypic loci, some genomic features, and to date have named more than 8,500 human non-protein coding RNA (ncRNA) genes and ncRNA pseudogenes. HGNC has already established unique names for most of the small ncRNA genes by working with experts for each class. Small ncRNAs can be defined into their respective classes by their shared homology and common function.

In contrast, long non-coding RNA (lncRNA) genes represent a disparate set of loci related only by their size, more than 200 bases in length, share no conserved sequence homology, and have variable functions. As with pc genes, wherever possible, lncRNAs are named based on the known function of their product; a short guide is presented herein to help authors when developing novel gene symbols for lncRNAs with characterised function. Researchers must contact the HGNC with their suggestions prior to publication, to check whether the proposed gene symbol can be approved. Although thousands of lncRNAs have been predicted in the human genome, for the vast majority their function remains unresolved. lncRNA genes with no known function are named based on their genomic context. Working with lncRNA researchers, the HGNC aims to provide unique and, wherever possible, meaningful gene symbols to all lncRNA genes.

lncRNA

  • Wright MW. (2014) A short guide to long non-coding RNA gene nomenclature. Hum Genomics 8(1), 7. [abstract]

Regulation of metabolism by long, non-coding RNAs

Our understanding of genomic regulation was revolutionized by the discovery that the genome is pervasively transcribed, giving rise to thousands of mostly uncharacterized non-coding ribonucleic acids (ncRNAs). Long, ncRNAs (lncRNAs) have thus emerged as a novel class of functional RNAs that impinge on gene regulation by a broad spectrum of mechanisms such as the recruitment of epigenetic modifier proteins, control of mRNA decay and DNA sequestration of transcription factors. The authors review those lncRNAs that are implicated in differentiation and homeostasis of metabolic tissues and present novel concepts on how lncRNAs might act on energy and glucose homeostasis. Finally, the control of circadian rhythm by lncRNAs is an emerging principles of lncRNA-mediated gene regulation.
lncRNA

  • Kornfeld JW, Brüning JC. (2014) Regulation of metabolism by long, non-coding RNAs. Frontiers in Genetics [Epub ahead of print]. [article]