Abstract
The development of high-throughput RNA structure profiling methods in the past decade has greatly facilitated our ability to map and characterize different aspects of RNA structures transcriptome-wide in cell populations, single cells and single molecules. The resulting high-resolution data have provided insights into the static and dynamic nature of RNA structures, revealing their complexity as they perform their respective functions in the cell. In this Review, we discuss recent technical advances in the determination of RNA structures, and the roles of RNA structures in RNA biogenesis and functions, including in transcription, processing, translation, degradation, localization and RNA structure-dependent condensates. We also discuss the current understanding of how RNA structures could guide drug design for treating genetic diseases and battling pathogenic viruses, and highlight existing challenges and future directions in RNA structure research.
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Acknowledgements
This work was supported by the UK Biotechnology and Biological Sciences Research Council (BBSRC) (BB/X01102X/1) and European Research Council (ERC) (selected by the ERC, funded by BBSRC Horizon Europe Guarantee (EP/Y009886/1)) (Y.D. and Y.Z.). Y.W. and X.C. are supported by funding from A*STAR, the National Research Foundation of Singapore, the EMBO Young Investigator Programme and a CIFAR Azrieli global scholar fellowship.
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Glossary
- Aptamer domain
-
An RNA structure in a riboswitch that binds to small molecules.
- Enzymatic structure probing
-
Refers to the use of nucleases that cleave RNA selectively at single-stranded or double-stranded regions (for example, RNase T1 and RNase V1, respectively); the resulting digestion footprints of the RNA can chart its structure.
- i-Motifs
-
Cytosine-rich DNAs that form quadruplex structures; also known as intercalated-motif DNAs.
- Riboswitches
-
Highly folded segments of (mostly bacterial) mRNAs that, when bound by environmental small molecules, induce structure changes that regulate the transcription or translation of the mRNA.
- R-loop structure
-
A three-stranded nucleic acid structure composed of a DNA–RNA hybrid and a displaced single strand of DNA.
- Small nucleolar RNAs
-
A class of small non-coding RNAs (ncRNAs) that mostly reside in nucleoli, which guide chemical modifications of other RNA species such as ribosomal RNAs.
- Stress granules
-
Dynamic cytoplasmic bodies formed in response to cellular stress, comprising RNA molecules and various proteins; they have a role in RNA metabolism and are associated with responses to environmental stresses.
- Upstream open reading frames
-
(uORFs). Open reading frames (ORFs) located upstream of a main open reading frame, that is, within the 5′ untranslated region (UTR) of the mRNA. uORFs can encode small peptides, and can regulate the translation of the main ORF by competing for the translation machinery.
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Cao, X., Zhang, Y., Ding, Y. et al. Identification of RNA structures and their roles in RNA functions. Nat Rev Mol Cell Biol (2024). https://doi.org/10.1038/s41580-024-00748-6
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DOI: https://doi.org/10.1038/s41580-024-00748-6
