Cryo-EM advances in RNA structure determination

Cryo-electron microscopy (cryo-EM) has emerged as an unprecedented tool to resolve protein structures at atomic resolution. Structural insights of biological samples not accessible by conventional X-ray crystallography and NMR can be explored with cryo-EM because measurements are carried out under near-native crystal-free conditions, and large protein complexes with conformational and compositional heterogeneity are readily resolved. RNA has remained underexplored in cryo-EM, despite its essential role in various biological processes. This review highlights current challenges and recent progress in using cryo-EM single-particle analysis to determine protein-free RNA structures, enabled by improvement in sample preparation and integration of multiple structural and biochemical methods.

Automated summary

Cryo-electron microscopy is an unprecedented tool for resolving protein structures at atomic resolution. It offers advantages in exploring biological samples inaccessible by conventional methods, especially in resolving conformational and compositional heterogeneity of large protein complexes. However, there are still challenges and limitations in using cryo-electron microscopy to study RNA structures.