Showing 3 ideas for tag "rna"

Goal 2: Reduce Human Disease

The relationship between genetic variation and disease mechanisms

What is the contribution of individual differences in RNA processing to disease causation, disease modification, disease susceptibility, and positive or negative responses to therapies? Studies using genome sequencing combined with RNA-seq have determined that genetic variation affects regulation of RNA processing as frequently as transcriptional regulation. While transcriptional networks are well defined in heart development... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

There are two areas of impact. First is to develop a better understanding between the effect of genetic variation on RNA processing and how individual differences in RNA processing translate into "phenotype" such as disease causation, disease modification, disease susceptibility, and positive or negative responses to therapies. Genes are filled with cis acting elements that are required for specific patterns of RNA processing. Variation that affects these cis elements are now known to produce different splice variants or mRNAs with different stabilities between individuals. This mechanism translating genotype to phenotype has not been explored. Second is to understand the RNA processing networks as well as we understand transcriptional networks during heart development and in heart disease. This understanding is very likely to provide previously unknown therapeutic approaches and targets.

Feasibility and challenges of addressing this CQ or CC

The high through put approaches available to compare genome and transcriptome sequences,computational approaches to predict the cis elements for RNA processing, high throughput analysis for RNA binding proteins and RNA structure have provided the tools necessary to perform genome-transcriptome comparisons as a starting point. Current exome/genome analysis ignores the influence of genetic variation in RNA processing. The tools are available. The first challenge is to decide on the question and there are two areas: One- what is the role of RNA processing in heart disease/how can RNA processing be used as a therapeutic target and Two - how much does differences in RNA processing (in addition to transcription) contribute to individual phenotypic differences relevant to disease?

Name of idea submitter and other team members who worked on this idea Tom Cooper

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Goal 1: Promote Human Health

Role of non-coding RNAs in cardiovascular biology and disease

Noncoding RNAs field is still in its infancy. It includes microRNA and long-non-coding RNA. Recent studies show that Non-coding RNA play important roles in the regulation of tissue homeostasis and pathophysiological conditions.
miRNA-based therapeutics showed promising results in numerous animal models of heart failure, cardiac hypertrophy, fibrosis and hyperlipidaemias, and showed success in in-human clinical trial... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Genetic studies using gain- or loss-of- function approaches suggest that lncRNAs can indeed contribute to cardiac or vascular dysfunction. Moreover, targeting of lncRNAs in a cell-selective manner might be possible to treat cardiovascular disease. This may open up the opportunity for the development of new therapeutic strategies.

Feasibility and challenges of addressing this CQ or CC

The regulation of lncRNAs has been documented in different disease models however the function is only known for a few lncRNAs. The fact that most lncRNAs are poorly conserved and are expressed as various transcript variants challenges the identification of specific biological functions and mechanisms of action. Combination of microRNA target sequesnces and long-non-coding RNA may allow for a novel cell-selective therapies.

Name of idea submitter and other team members who worked on this idea Hana Totary-Jain

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Goal 1: Promote Human Health

Emerging importance of RNA regulation

What are the roles of RNAs (e.g., microRNAs, long non-coding RNAs, etc.) in myocardial growth, adaptation, and injury healing response?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

As an example, recent studies suggest key regulatory roles of RNAs (e.g., microRNAs and long non-coding RNAs) in cardiac pathological hypertrophy and heart failure. Better understanding of such mechanisms will spur development of new therapies based on these mechanisms.

Feasibility and challenges of addressing this CQ or CC

Most of the infrastructure and methods are in place. There appears to be growing interest and excitement about the potential of this research area. However, this field needs more researchers.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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