Hypoplastic left heart syndrome (HLHS) is a fatal congenital heart disease in which the left side of the heart is underdeveloped, impairing the systemic circulation. Underdeveloped left ventricle exerts biomechanical stress on the right ventricle that can progress into heart failure. Genome-wide transcriptome changes have been identified at early stages in the right ventricle (RV) of infants with HLHS, although the molecular mechanisms remain unknown. Here, we demonstrate that the RNA binding protein Rbfox2, which is mutated in HLHS patients, is a contributor to transcriptome changes in HLHS patient RVs. Our results indicate that majority of transcripts differentially expressed in HLHS patient hearts have validated Rbfox2 binding sites. We show that Rbfox2 regulates mRNA levels of targets with 3'UTR binding sites contributing to aberrant gene expression in HLHS patients. Strikingly, the Rbfox2 nonsense mutation identified in HLHS patients truncates the protein, impairs its subcellular distribution and adversely affects its function in RNA metabolism. Overall, our findings uncover a novel role for Rbfox2 in controlling transcriptome in HLHS.
Pharmacology, Toxicology and Pharmaceutical Science
2
5%
Engineering
2
5%
Other
3
7%
Unknown
16
36%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 June 2018.
All research outputs
#15,380,722
of 22,881,964 outputs
Outputs from Scientific Reports
#78,001
of 123,614 outputs
Outputs of similar age
#238,141
of 367,231 outputs
Outputs of similar age from Scientific Reports
#2,245
of 3,683 outputs
Altmetric has tracked 22,881,964 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 123,614 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one is in the 29th percentile – i.e., 29% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 367,231 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3,683 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.
