| First Author | Xue Z | Year | 2016 |
| Journal | Mol Cell | Volume | 64 |
| Issue | 1 | Pages | 37-50 |
| PubMed ID | 27618485 | Mgi Jnum | J:248787 |
| Mgi Id | MGI:6094800 | Doi | 10.1016/j.molcel.2016.08.010 |
| Citation | Xue Z, et al. (2016) A G-Rich Motif in the lncRNA Braveheart Interacts with a Zinc-Finger Transcription Factor to Specify the Cardiovascular Lineage. Mol Cell 64(1):37-50 |
| abstractText | Long non-coding RNAs (lncRNAs) are an emerging class of transcripts that can modulate gene expression; however, their mechanisms of action remain poorly understood. Here, we experimentally determine the secondary structure of Braveheart (Bvht) using chemical probing methods and show that this approximately 590 nt transcript has a modular fold. Using CRISPR/Cas9-mediated editing of mouse embryonic stem cells, we find that deletion of 11 nt in a 5' asymmetric G-rich internal loop (AGIL) of Bvht (bvht(dAGIL)) dramatically impairs cardiomyocyte differentiation. We demonstrate a specific interaction between AGIL and cellular nucleic acid binding protein (CNBP/ZNF9), a zinc-finger protein known to bind single-stranded G-rich sequences. We further show that CNBP deletion partially rescues the bvht(dAGIL) mutant phenotype by restoring differentiation capacity. Together, our work shows that Bvht functions with CNBP through a well-defined RNA motif to regulate cardiovascular lineage commitment, opening the door for exploring broader roles of RNA structure in development and disease. |
