There is growing evidence that transcription and nuclear organization are tightly linked. Yet, whether transcription of thousands of long noncoding RNAs (lncRNAs) could play a role in this packaging process remains elusive. Although some lncRNAs have been found to have clear roles in nuclear architecture (e.g., FIRRE, NEAT1, XIST, and others), the vast majority remain poorly understood.
In this Perspective, Researchers from Harvard University highlight how the act of transcription can affect nuclear architecture. They synthesize several recent findings into a proposed model where the transcription of lncRNAs can serve as guide-posts for shaping genome organization. This model is similar to the game “cat’s cradle,” where the shape of a string is successively changed by opening up new sites for finger placement. Analogously, transcription of lncRNAs could serve as “grip holds” for nuclear proteins to pull the genome into new positions. This model could explain general lncRNA properties such as low abundance and tissue specificity. Overall, the authors propose a general framework for how the act of lncRNA transcription could play a role in organizing the 3D genome.
The Cat’s Cradle Model
In a specific cell state, DNA is folded in a specific 3D conformation (i). Then, transcription of lncRNAs in specific DNA regions (ii) marks the spot for specific proteins to bind (iii) and pull the DNA to a new conformation (iv). Similarly, at the beginning of the cat’s cradle game, the string is folded in a specific conformation (i). Then, another person’s fingers grip to specific string locations (ii) and pull (iii) to form a new string conformation (iv). It is important to notice that this representation is a cartoon and that the size of proteins/hands and DNA/string has been magnified for simplicity.