Species: Mus musculus

Position: chr18: 61639541-61647485

Known as: Bvht , ENSMUSG00000098098

Transcript: NR_045420 , ENSMUST00000183087 , ENSMUST00000183083

Sequence: Display Download

Description:

The mouse lncRNA Braveheart (Bvht) appears to act in trans to regulate cardiovascular lineage commitment. According to SHAPE and DMS probing, the secondary structure of in vitro transcribed full-length Bvht (~590 nt) is organized into a highly modular structure including a 50 asymmetric G-rich internal loop (AGIL). By CRISPR/Cas9-mediated homology-directed repair to knockout this loop (denoted bvhtdAGIL) in mouse ESCs (mESCs), it was showed that the AGIL motif is necessary for cardiomyocyte (CM) differentiation, along with key cardiac transcription factors (TFs) failing to activate during the transition from nascent mesoderm to the cardiac progenitor (CP) state. The AGIL motif interacts with a small subset of factors including the heart-expressed zinc-finger TF cellular nucleic acid binding protein (CNBP/ZNF9), known to bind G-rich single-stranded nucleic acids. CNBP represses CM differentiation and that loss of CNBP partially rescues the bvhtdAGIL phenotype, suggesting that these factors function together to specify the cardiovascular lineage. These results show how a small RNA motif in Bvht can direct cell fate and demonstrate that structural studies combined with genetic perturbation can provide critical insights into lncRNA function.

1. Xue Z, Hennelly S, Doyle B, Gulati AA, Novikova IV, 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.