Looking at long non-coding RNAs from a 3D structural perspective

Noncoding RNAs accomplish a remarkable variety of biological functions. From the regulation of gene expression to translation and even the protection of genomes from foreign nucleic acids. Among them, long non-coding RNA (lncRNA) are regulating RNAs of large size (> 1000 nucleotides) that are involded in disease prevention but their function as well as three-dimensional structures remain poorly characterized. A recent study has demonstrated the role of local structural elements of the maternally-expressed gene 3 (MEG3) that potentiates protein p53, a key transcription factor controlling cell proliferation, whose role is to arrest the growth of unhealthy cells before they degenerate into cancerous tissues (Uroda T, Anastasakou E, Rossi A, Teulon J-M, Pellequer J-L, Annibale P, Pessey O, Inga A, Chillon I and Marcia M (2019) Conserved pseudoknots in lncRNA MEG3 are essential for stimulation of the p53 pathway. Mol. Cell 75: 1-14. DOI:10.1016/j.molcel.2019.07.025).

In a collaborative work between the European Molecular Biology Laboratory (EMBL) in Grenoble with colleagues at the Max Delbruck Center in Berlin and the Institut de Biologie Structurale (CEA/CNRS/UGA) in Grenoble, researchers used complementary well established structural biology techniques to characterize the shape of lncRNA: atomic force microscopy, which identified captured individual RNA particles and inferred their size and compactness; and small angle X-ray scattering, which characterized the RNA 3D shape in solution. The description of this new approach has been presented in a recent issue of Nature Protocols. This protocol is likely applicable to other long RNA molecules such as the untranslated RNAs (UTR) present in large RNA genome of viruses (details).

Visualizing the functional 3D shape and topography of long non coding RNAs by single-particle atomic force microscopy and in solution hydrodynamic techniques. Uroda T, Chillon I, Annibale P, Teulon JM, Pessey O, Karuppasamy M, Pellequer JL, Marcia M. Nature Protocols; doi: 10.1038/s41596-020-0323-7