Long Noncoding Rna Braveheart Health Public Impact Analysis - What the Scientific Implications of This Paper Are for Public Health.

Topic: What the scientific implications of this paper are for public health.

This paper aims to underline some of the scientific implications the article “Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment” by Klattenhoff, Carla A. et al. (2013) may have on public health. First, I will attempt to summarize the article and then I will explain my ideas of its scientific implications.

The authors draw our attention as to how important it is to understand the mechanism through which pluripotent cells differentiate into cardiac cells.  Knowing which and how molecules participate in the control of heart development will allow us to come up with a better treatment for congenital heart conditions.

One of the molecules the authors mention is MESP1. This molecule, which is a transcription factor, participates in heart development by marking cells to become cardiac cells. MESP1 controls heart development by regulating other transcription factors, as well as Snai and Twist gene that participate in epithelial-mesenchymal transition. In addition, the authors are interested in another molecule that regulate this transition such as the long noncoding RNA (lncRNA).

Some previous knowledge about this molecule is highlighted in the paper: lncRNAs are more than 200 nucleotides long, they can regulate gene expression, and many are species-specific. They are not as conserved as coding RNAs, their expression pattern varies in different tissues, they promote or suppress differentiation in somatic cells, and they are involved in lineage commitment. The authors seek to better understand these mechanisms and the role of these lncRNAs.

The first experiment aimed to identify the candidate lncRNAs involved in cardiac cell differentiation. In order to do that, the authors analyzed, through RNA-seq, the lnRNA expression in all three murine embryonic germ layers. Among the 47 candidates with high expression in embryonic stem cells (ESC), they found out that the candidate AK143260 (Braveheart) is highly expressed in the heart in comparison to the other tissues. They validated the identification of the lncRNA through the RACE (rapid amplification of cDNA ends) method which revealed ~590 nucleotides. Another lncRNA confirmation finding is that Bvht is not translated into protein. Other analysis revealed that this lncRNA might be mouse-specific.

Next, they checked the function of Bvht in lineage commitment. They generated mouse embryonic stem cell lines that express short hairpin RNA against Bvht. Through qRT-PCR and northern blot they noticed depletion of ~80% of Bvht. However, the depletion did not affect cell morphology of undifferentiated cells from the three germ layers. The authors concluded that self-renewal of these cells do not require Bvht. In contrast, they found out that Bvht is necessary for cardiac muscle differentiation when they tested contraction of embryonic bodies (EBs) composed of Bvht-depleted cells.