NEWS & EVENTS

Role of Long Non-coding RNA in Cardiovascular, Lung, and Blood Diseases

June 1 - 2 , 2016
NIH
Bethesda, MD

Description

The National Heart, Lung, and Blood Institute convened a Working Group (WG) on June 1-2, 2016 in Bethesda, Maryland, to discuss Role of Long Non-coding RNA in Cardiovascular, Lung, and Blood Diseases.

While significant ongoing efforts continue to focus on the molecular basis of various cardiovascular and lung diseases at the gene and protein levels, relatively less effort has centered on exploration of gene transcription regulation by the non-coding portion of the genome.  Advances in basic biology combined with recent whole genome and transcriptome studies demonstrate that the control of protein expression is far more dynamic and complex than previously assumed.  Emerging evidence suggests a significant portion of the non-coding transcripts function as regulators of gene expression, translation, post-translational modifications, differentiation, and signaling during development and under pathological conditions.  In recent years, there has been increasing recognition that miRNAs have important roles in HLBS biology, however, little is known about the function of long non-coding RNA (lncRNA) despite the increasing numbers of lncRNAs identified in the human genome.  Hence a Working Group encompassing basic and clinical science along with emerging technologies expertise was convened to examine (1) the current state of the lncRNA in the cardiovascular, lung, and blood diseases and (2) gaps in knowledge, technology, tools, and other barriers necessary to move the field forward.

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Recap

Discussions and Recommendations

The WG discussions were centered on the following areas:

1. Identification of lncRNA

Mining existing databases and annotating untranscribed regions of the genome were discussed. Challenges to distinguishing lncRNAs signals from noise due to their low abundance were discussed. The Group highlighted issues related to functional validation, finding orthologs, and the lack of a systematic lncRNA annotation protocol in current databases.

2. Expression of lncRNA

The Working Group discussed the need for developmental stage-specific and tissue/cell-specific expression of lncRNAs and the inherent challenges given the very low levels of expression.  The need for more innovative technologies and approaches in addition to single cell analysis and imaging approaches were also discussed.  LncRNAs may also be detected in plasma or other body fluids, suggesting their transportation may reflect pathophysiological processes of clinical interest. Many lncRNAs have been described as biomarkers of other diseases, such as cancer, and there is expectation that similar findings will emerge in disorders of the heart, vasculature, lung, and blood.

3. Biological functions of lncRNA

The Group reiterated the importance of lncRNAs in diverse biological processes acknowledging that understanding biological function of lncRNA represents a formidable challenge.  The effects of lncRNA may be subtle and only observable under specific conditions.  It is also hard to knock out specific lncRNAs in animal models without off-target effects because lncRNA sometimes locate within other functionally important regions. The Group stressed the need to develop new tools and reagents to help identify lncRNA binding partners, in order to gain crucial insights into functional implications.  The Group emphasized the need for several complementary methods to verify binding and interaction.  The Group also felt that one of the biggest limitations to gaining functional insights from human studies is the lack of high quality biospecimens suitable for RNA research.

Working Group Recommendations

  • Facilitate development of novel technologies and tools to capture interactions of noncoding RNAs with other macromolecules, and characterize the functional conservation rules of lncRNAs among species

  • Help adapt existing molecular biology tools to investigate the basic biology of lncRNAs and support development of high-throughput functional screens and bioinformatic tools

  • Support development of physiologically relevant experimental model systems to study in vivo functions of lncRNAs relevant to NHLBI’s mission integrating both basic and clinical science approaches

  • Encourage identification of disease associated lncRNA mutations using biospecimens from population studies

  • Ensure that biospecimens from NHLBI supported clinical studies are amenable for RNA profiling through establishment of quality metrics on collection, storage, and transportation

  • Disseminate information regarding available NHLBI biospecimens and associated sequence data

  • Promote training for the next generation of scientists to mine human RNAseq data

Publication Plans

The working group plans to prepare two manuscripts for publication in peer-reviewed journals.