RNA folding articles from across Nature Portfolio

Methodological advances have enabled discoveries of RNA polymerase interactions with RNA processing machineries, such as the splicing and 3′-end cleavage machineries. This Review discusses the roles of these interactions in gene regulation and eukaryotic cellular stress responses, and highlights parallels between co-transcriptional RNA processing in eukaryotes and prokaryotes.

Here, the authors present eSPET-seq a method to measure cotranscriptional RNA folding in eukaryotes. Further analysis reveals an antimutagenic effect of nascent RNA folding and contribution to the variability of local mutation rates across the yeast genome.

All aspects of gene regulation involve RNA helicases, which bind or remodel RNA and RNA–protein complexes. Recent data establish a link between helicase structure, mechanism of function and biological roles, including in diseases such as cancer and neurological disorders, with implications for the design of small-molecule inhibitors.

rG4s are G-quadruplex structures found in transcriptome. Many RNAs can fold into rG4s in vitro, yet their folding and functions in vivo are not well understood. Here the authors showed that rG4s folding is dynamically regulated under stress in human cells.

Cruz et al. present cryo-EM structures of large ribosomal subunit assembly intermediates that reveal how the DEAD-box helicase Spb4 remodels rRNA secondary structures to facilitate and guide 60S maturation.

Leilei Chen describes the discovery that adenosine-to-inosine editing by ADAR1 marks endogenous double-stranded RNA as self, to prevent it from triggering innate immunity.

The effects of RNA secondary structure on translation have been well recognized; however, the global interplay between both in a dynamic cellular system is poorly understood. Beaudoin, Giraldez and colleagues have analyzed RNA structure dynamics during zebrafish embryonic development and have found that the ribosome unzips mRNA secondary structure during translation, thus leading to a global decrease of structure in highly translated transcripts. Furthermore, the authors establish RNA structure in the 3′ untranslated regions of mRNAs as a major regulator of transcript stability in this context.

Assembly of the small ribosomal subunit from an RNA strand and 33 proteins is an intricate and dynamic process. Two cryo-EM studies now provide insight into a complicated complex of at least 51 trans-factors that act on the preribosomal small subunit to sequentially fold it into a 3D molecular machine.

A new mechanism of controlling translation initiation depends on DEAD-box RNA helicases and on RNA structures, including those present in coding sequences.