MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures

Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. Researchers More »

LncRNA Regulator Of Brown Fat Identified

from Asian Scientist AsianScientist (Apr. 29, 2015) – A study by researchers in Duke-NUS Graduate Medical School Singapore (Duke-NUS) has More »

An update on LNCipedia – a database for annotated human lncRNA sequences

LNCipedia collects long non-coding RNA sequences and annotation from different sources. In version 3.0, over 90,000 new transcripts were added More »

Unveiling a new factor that helps breast cancer cells to tolerate drugs

from biotechin.asia by Mohamad Moustafa Ali Breast cancer is one of the most divergent and heterogeneous genetic disorders that affects More »

Dynamic and widespread lncRNA expression in the sponge and the origin of animal complexity

Long non-coding RNAs (lncRNAs) are important developmental regulators in bilaterian animals. A correlation has been claimed between the lncRNA repertoire More »

 

Upcoming Webinar – Knockdown of lncRNAs: exploring RNAi and antisense oligo methods

lncRNADate: Tuesday, August 25, 2015

Time: Session 1: 9:00–10:00 am CDT (UTC-5)
Session 2: 1:00–2:00 pm CDT (UTC-5)

Presenter: Kim Lennox, MSc

Program overview

Thousands of different long non-coding RNAs (lncRNAs) exist in mammalian cells. lncRNAs do not encode proteins but can be very important for cell function. Studying their functions can be difficult because of their diverse modes of action. One method to discern cellular function is by selective knockdown of a specific lncRNA species. However, achieving consistent knockdown has proven to be more challenging for lncRNAs than for mRNAs or miRNAs. In this webinar, we will discuss some of the issues encountered with lncRNA research. We will cover antisense oligonucleotide (ASO) and small interfering RNA (siRNA) methods for lncRNA knockdown. And, we will show how cellular localization of a specific lncRNA target informs the choice of knockdown method.

About the Presenter

Kim Lennox has been a research scientist in the Molecular Genetics group at IDT for 13 years. She studied genetics at Iowa State University and received an MSc in Biomolecular Archaeology from the University of Manchester (UK). Kim is an expert at using synthetic oligonucleotides to suppress gene expression and is a co-author on 17 scientific papers describing various methods of gene knockdown. Her recent publications describe optimization of antisense oligonucleotides and siRNAs to degrade mRNAs and long non-coding RNAs (lncRNAs). She also has published work characterizing steric blocking antisense oligonucleotides, such as anti-miRNA oligonucleotides (AMOs) and splice-switching oligonucleotides (SSOs).

REGISTER

Featured lncRNA – PCAT5

Castration-resistant prostate cancer (CRPC) that arise after the failure of androgen blocking therapies cause most of the deaths from prostate cancer (PC), intensifying the need to fully understand CRPC pathophysiology.

A team led by researchers at MD Anderson Cancer Center characterized the transcriptomic differences between untreated PC and locally recurrent CRPC and they report the identification of 145 previously unannotated intergenic long non-coding RNA transcripts (lncRNA) or isoforms that are associated with PC or CRPC. Of the one-third of these transcripts that were specific for CRPC, they defined a novel lncRNA termed PCAT5 as a regulatory target for the transcription factor ERG, which is activated in ~50% of human PC. Genome-wide expression analysis of a PCAT5-positive PC after PCAT5 silencing highlighted alterations in cell proliferation pathways. Strikingly, an in vitro validation of these alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, colony-forming potential and apoptosis.

lncRNA

Expression level characterization of prostate cancers.

These findings reveal a key molecular determinant of differences between PC and CRPC at the level of the transcriptome. Further, they establish PCAT5 as a novel oncogenic lncRNA in ERG-positive prostate cancers, with implications for defining CRPC biomarkers and new therapeutic interventions.

  • Ylipää A, Kivinummi K, Kohvakka A, Annala M, Latonen L, Scaravilli M, Kartasalo K, Leppänen SP, Karakurt S, Seppälä J, Yli-Harja O, Tammela TL, Zhang W, Visakorpi T, Nykter M. (2015) Transcriptome sequencing reveals PCAT5 as a novel ERG-regulated long non-coding RNA in prostate cancer. Cancer Res [Epub ahead of print]. [abstract]

mi & lncRNA World 2015 Conference

lncRNA

Deepen Your Mechanistic Understanding to Harness the Biomarker, Diagnostic & Therapeutic Applications of mi & lncRNA’s

mi & lncRNA World 2015 will enable you to deepen and broaden your understanding of miRNA and lncRNA mechanisms and functionality. Heighten your focus on the basic, translational, and clinical opportunities of non-coding entities to bridge the gap between basic research and clinical relevance.

With the lncRNA field experiencing an explosion in publications and scientific breakthroughs, mi & lncRNA World 2015 will enable you to understand the fundamental biology and early applications across a spectrum of diseases. Understand how ground-breaking opportunities in miRNA biomarker-targeted research, drug and diagnostic development are being uncovered at an ever-increasing rate.

Channel the latest scientific breakthroughs as you:

  1. Rapidly advance your understanding of the underlying fundamental biology of miRNA’s and lncRNA’s through greater understanding of mechanisms, biogenesis and functionality
  2. Refine the established application of miRNA’s as biomarkers and diagnostic entities with particular focus on blood-based and exosomal vesicles
  3. Bridge the knowledge gap between lncRNA discovery and validation to ensure progression of your most promising candidates through your research and development pipeline
  4. Overcome the key miRNA therapeutic specific challenges, including breaking through the delivery bottleneck and optimizing compound efficacy and safety
  5. Uncover the early biomarker, diagnostic and therapeutic applications of lncRNA’s as understanding of non-coding functionality exponentially increases

Download brochure

MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures

lncRNA

Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. Researchers from the University of Gothenburg have used chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify 276 lncRNAs enriched in repressive chromatin from breast cancer cells.

Using one of the chromatin-interacting lncRNAs, MEG3,  they explored the mechanisms by which lncRNAs target chromatin. They show that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-β genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA-DNA triplex formation. The researchers have found that RNA-DNA triplex structures are widespread and are present over the MEG3 binding sites associated with the TGF-β pathway genes. These findings suggest that RNA-DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs.

  • Mondal T, Subhash S, Vaid R, Enroth S, Uday S, Reinius B, Mitra S, Mohammed A, James AR, Hoberg E, Moustakas A, Gyllensten U, Jones SJ, Gustafsson CM, Sims AH, Westerlund F, Gorab E, Kanduri C. (2015) MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures. Nat Commun 6:7743. [article]

Predicting the Functions of Long Noncoding RNAs Using RNA-Seq

Long noncoding RNAs (lncRNAs) have been shown to play key roles in various biological processes. However, functions of most lncRNAs are poorly characterized. Here, researchers from Harbin Medical University present a framework to predict functions of lncRNAs through construction of a regulatory network between lncRNAs and protein-coding genes. Using RNA-seq data, the transcript profiles of lncRNAs and protein-coding genes are constructed. Using the Bayesian network method, a regulatory network, which implies dependency relations between lncRNAs and protein-coding genes, was built. In combining protein interaction network, highly connected coding genes linked by a given lncRNA were subsequently used to predict functions of the lncRNA through functional enrichment. Application of this method to prostate RNA-seq data showed that 762 lncRNAs in the constructed regulatory network were assigned functions. The researchers found that lncRNAs are involved in diverse biological processes, such as tissue development or embryo development (e.g., nervous system development and mesoderm development). By comparison with functions inferred using the neighboring gene-based method and functions determined using lncRNA knockdown experiments, this method can provide comparable predicted functions of lncRNAs. Overall, this method can be applied to emerging RNA-seq data, which will help researchers identify complex relations between lncRNAs and coding genes and reveal important functions of lncRNAs.

rna-seq

  • Xiao Y, Lv Y, Zhao H, Gong Y, Hu J, Li F, Xu J, Bai J, Yu F, Li X. (2015) Predicting the Functions of Long Noncoding RNAs Using RNA-Seq Based on Bayesian Network. Biomed Res Int 2015:839590. [article]