Cardiac development is anchored on an intricate program of gene regulation and coordination, associated with critical timing and cell–cell interactions. Rather than a single master regulatory process, as originally envisioned to reside in a transcriptional complex or protein signaling cascade, cardiac development is likely regulated by a network of coordinated gene expressions, critically timed, and calibrated. Noncoding RNAs (ncRNA) are now seen as key new players in this regulatory network, and the road map is only beginning to be constructed.
Cardiovascular diseases often recapitulate cardiac development when the cardiovascular systems sustain stress or injury. Searches for disease-associated genes often ended up in the noncoding intergenic regions of the genome where ncRNAs are often expressed (eg, 9p21 chromosomal region for atherosclerosis). Thus, the role of ncRNAs in the pathogenesis of diseases has assumed an increasing importance, even though the full mechanistic understanding is yet to evolve.
Long noncoding RNAs (lncRNA) are RNA transcripts longer than 200 nucleotides expressed by the genome, but do not themselves code proteins. They are transcribed across the genome, including the intergenic regions as potentially overlapping sense and antisense transcripts that can flank protein-coding genes. Coordinated activities of lcnRNAs likely play a major role in the regulatory networks of organ development, normal organ function, and disease pathogenesis.
Until recently, ncRNAs were considered generic regulators of cell function, controlling the basic pathways of mRNA splicing and protein translation. However, in the past 10 years large scale community projects such as ENCODE (Encycopdia of DNA (read more…)
Long noncoding RNAs (lncRNA) are differentially activated at the fetal and adult stages of cardiac development. Possible mechanisms by which lncRNAs can modulate gene expression include mRNA decay, mRNA stabilization, or microRNA (miRNA) sponge during the transition from fetal to adult heart. Epigenetic changes promote the expression of lncRNAs (H3K4me1 as enhancers and H3K4me3 as promoters) and their coordinate mRNA. In the fetal heart, lncRNAs associate more with genes involved in development and programming, whereas in the adult heart lncRNAs associate more with genes involved in disease and dysfunction.