A team of researchers has pieced together the structure of a type of long noncoding RNA. By analyzing the structure of the molecule, scientists are beginning to understand how it functions. The findings are in a paper that was just published in the journal Molecular Cell.
Scientists discovered long non-coding RNAs (lncRNAs) less than a decade ago and the molecules are still poorly understood. Unlike regular RNA, these strands don’t code for any proteins. However, past research has shown that they still somehow affect gene expression. In 2013, an lncRNA called Braveheart (Bvht) was isolated in mice. The molecule was shown to be necessary for the proper development of heart muscles but the actual mechanisms were unknown.
A research team from the Massachusetts Institute of Technology used a method called chemical probing to determine the structure of Bvht. They exposed the lncRNA to chemicals that would modify the nucleotides in a way that would allow them to map out the structure. The team was able to identify various structural regions throughout the molecule, including double-stranded helices and loops.
The researchers then tried to determine which regions were most important to the function of Bvht. Interestingly, a single loop consisting of only 11 nucleotides was critical to the development of normal heart cells. Removing this segment immediately stops heart cell development. The team also discovered that a protein called cellular nucleic acid binding protein (CNBP) interacted with the loop. Mutations in CNBP are already known to cause heart defects in both humans and mice. The researchers investigated further and found that Bvht releases a molecule that represses CNBP, allowing cells to grow into heart muscle. Without Bvht, CNBP blocks the formation of heart cells.
The team plans to analyze the structure of human lncRNAs next to look for similarities in function. The authors believe that understanding lncRNAs will allow for new breakthroughs in medical research and medicine.
Zhihong Xue et al. A G-Rich Motif in the lncRNA Braveheart Interacts with a Zinc-Finger Transcription Factor to Specify the Cardiovascular Lineage. Molecular Cell (2016).