A lncRNA Perspective into (Re)Building the Heart

Abstract

Our conception of the human genome, long focused on the 2% that codes for proteins, has profoundly changed since its first draft assembly in 2001. Since then, an unanticipatedly expansive functionality and convolution has been attributed to the majority of the genome that is transcribed in a cell-type/context-specific manner into transcripts with no apparent protein coding ability. While the majority of these transcripts, currently annotated as long non-coding RNAs (lncRNAs), are functionally uncharacterized, their prominent role in embryonic development and tissue homeostasis, especially in the context of the heart, is emerging. In this review, we summarize and discuss the latest advances in understanding the relevance of lncRNAs in (re)building the heart.

Keywords: cardiac development; cardiac regeneration; cell-fate commitment; embryonic development; homeostasis; long non-coding RNAs.

Figure 1

Genomic contexts of lncRNAs & modes of action. (A) LncRNA genes (blue) can exist in various genomic contexts. The histone marks are similar to protein-coding genes. NcRNAs transcribed from enhancer regions are unique in their features. (B) Overview of the different interactions of lncRNAs and their target molecules.

Figure 2

Mammalian cardiac development in vivo/in vitro and consequences of aging on the heart. (A) Development of the mammalian heart is a complex series of events, marked by distinct morphological changes. Expression of selected lncRNAs is indicated along the developmental timeline. (B) During aging, the heart becomes hypertrophic, i.e., the heart muscle increases by an increase in cell size, not number. Furthermore, the risk of myocardial infarction (MI) increases with age. MI can eventually result in hypertrophy in order to compensate for the loss in heart muscle. Selected lncRNAs identified to play a role in infarction or hypertrophy are depicted.