Importance of lncRNA tertiary structure in key cellular processes

There are several cellular mechanisms to fight cancer. One of the major actors is the p53 protein which, when it becomes inactive, greatly increases the risk of cancer development. Maternally expressed 3 (MEG3), a long non-coding RNA (lncRNA, >500 kDa), is another molecule that prevents cancer through its stimulating activity on p53.
The results of a study on the structure of MEG3, published in Molecular Cell, could help to advance the diagnosis and treatment of certain types of cancer. It was led by Marco Marcia’s group (EMBL, Grenoble) in collaboration with the AFM team of the Institute of Structural Biology (IBS, Grenoble), the CIBIO department (University of Trento, Italy) and the Max Delbrück Center (Berlin).
This study shows that it is through a precise three-dimensional structure that MEG3 ensures its cellular function, in particular through very specific RNA structures known as "kissing loops".
The IBS AFM team determined by single lncRNA molecule imaging, the conformation of MEG3 under several experimental conditions (native, destabilizing, and denaturing). The attached figure provides a sample of 100 isolated molecules of native MEG3 deposited on mica and air-imaged by atomic force microscopy (AFM) with Peak-Force mode. Compared to AFM imaging of unstructured (poly-A) or known to be structured (group II intron) RNA molecules, the results demonstrate the presence of a particular folding for MEG3 which is consistent with the biochemical and biophysical results of this study.

Conserved pseudoknots in lncRNA MEG3 are essential for stimulation of the p53 pathway. Uroda T, Anastasakou E, Rossi A, Teulon J-M, Pellequer J-L, Annibale P, Pessey O, Inga A, Chillon I and Marcia M. Mol. Cell 75 : 1-14.