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| Open AccessHybrids of RNA viruses and viroid-like elements replicate in fungi
RNA viruses are defined by linear RNA genomes encoding an RNA-dependent RNA polymerase, while viroid-like elements consist of small, single-stranded, circular RNA genomes that, in some cases, encode self-cleaving catalytic RNAs. Here, the authors identify over 20,000 candidate viroid-like elements, and show that infectious agents of fungi display hybrid features of viroid-like RNAs and RNA viruses.
- Marco Forgia
- , Beatriz Navarro
- & Marcos de la Peña
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Article
| Open AccessChemical evolution of an autonomous DNAzyme with allele-specific gene silencing activity
Low activity currently prevents the wider use of DNA enzymes (DNAzymes). Here the authors report the chemical evolution of a DNAzyme with high catalytic activity under near physiological conditions: the enzyme achieves ~65 turnovers in 30 minutes.
- Kim Nguyen
- , Turnee N. Malik
- & John C. Chaput
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| Open AccessRibozyme-mediated RNA synthesis and replication in a model Hadean microenvironment
Non-equilibrium conditions at heated water-air interfaces can model Hadean microenvironments. Here, the authors show that such conditions enable one-pot synthesis, strand release and folding of functional RNAs similar to modern biological systems.
- Annalena Salditt
- , Leonie Karr
- & Hannes Mutschler
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| Open AccessSnapshots of the second-step self-splicing of Tetrahymena ribozyme revealed by cryo-EM
The Tetrahymena ribozyme changes conformations to perform its self-splicing function. Here, the authors capture six structural snapshots of ribozyme during the second step of self-splicing from a single specimen, revealing the structural basis of how it promotes and coordinates self-splicing reactions.
- Shanshan Li
- , Michael Z. Palo
- & Kaiming Zhang
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Article
| Open AccessPeriodic temperature changes drive the proliferation of self-replicating RNAs in vesicle populations
How primordial cells could achieve inheritance of encapsulated components is still an open question. Here, the authors show that ribozymes can assemble in active forms and replicate in populations of membrane vesicles thanks to freeze-thaw cycles.
- Elia Salibi
- , Benedikt Peter
- & Hannes Mutschler
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Article
| Open AccessExperimental exploration of a ribozyme neutral network using evolutionary algorithm and deep learning
Neutral networks, which are sets of genotypes connected via single mutations that share the same phenotype, are important for evolvability. Here, the authors provide experimental evidence of a neutral network in an RNA enzyme using a high-throughput assay and deep learning.
- Rachapun Rotrattanadumrong
- & Yohei Yokobayashi
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Article
| Open AccessStructural remodeling of ribosome associated Hsp40-Hsp70 chaperones during co-translational folding
Ribosome associated complex (RAC)- HSP70 (Ssb in yeast) is a eukaryotic chaperone system involved in co-translational folding. Here, authors report structures of RAC-containing ribosomal complexes, which suggest a working model for the dynamic actions of RAC-Ssb during the process.
- Yan Chen
- , Bin Tsai
- & Ning Gao
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Article
| Open AccessStructural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling
Maturation of the ribosomal peptidyl transferase center (PTC) is mediated by universally conserved GTPases. Here, cryo-EM structures of mitochondrial ribosomal large subunit assembly intermediates and of mature ribosomes offer insight into the roles of several assembly factors, including GTPBP6’s role in both ribosome biogenesis and recycling.
- Hauke S. Hillen
- , Elena Lavdovskaia
- & Ricarda Richter-Dennerlein
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Article
| Open AccessDarwinian properties and their trade-offs in autocatalytic RNA reaction networks
Autocatalytic networks may have started evolution during the origin of life. Here, the authors establish a landscape of thousands of RNA networks by barcoded sequencing and microfluidics, and derive relationships between topology and Darwinian properties such as variation and differential reproduction.
- Sandeep Ameta
- , Simon Arsène
- & Philippe Nghe
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Article
| Open AccessCryo-EM structure of catalytic ribonucleoprotein complex RNase MRP
Ribozyme-based RNase MRP is an essential eukaryotic enzyme involved in the maturation of rRNA and is evolutionarily related to RNase P. Here, the authors present the 3.0 Å cryo-EM structure of the S. cerevisiae RNase MRP holoenzyme, a 450 kDa ribonucleoprotein complex and compare it with RNase P.
- Anna Perederina
- , Di Li
- & Andrey S. Krasilnikov
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Article
| Open AccessComprehensive sequence-to-function mapping of cofactor-dependent RNA catalysis in the glmS ribozyme
RNA sequence-structure-function relationships can be studied via assays of variant activity. The authors developed a method to systematically determine ribozyme variant kinetics, using it to map double-mutant interactions and show that cleavage rate drives sequence conservation in the glmS ribozyme.
- Johan O. L. Andreasson
- , Andrew Savinov
- & William J. Greenleaf
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Article
| Open AccessHigh-throughput identification of synthetic riboswitches by barcode-free amplicon-sequencing in human cells
Riboswitches can mediate ligand-dependent RNA cleavage and splicing to control gene expression. Here the authors present a method to functionally screen large libraries and identify functional variants.
- Benjamin Strobel
- , Maike Spöring
- & Sebastian Kreuz
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Article
| Open AccessMassively parallel RNA device engineering in mammalian cells with RNA-Seq
Synthetic RNA-based devices can dynamically control a wide range of processes. Here the authors develop a quantitative and high-throughput mammalian cell-based RNA-seq assay to efficiently engineer ribozyme switches.
- Joy S. Xiang
- , Matias Kaplan
- & Christina D. Smolke
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Article
| Open AccessTemplate-directed RNA polymerization and enhanced ribozyme catalysis inside membraneless compartments formed by coacervates
Membraneless compartments have been theorized to be prebiotic micro-compartments as they spontaneously encapsulate RNA and proteins. Here, the authors report membraneless compartments can enhance RNA chemistries, affecting template directed RNA polymerization and stimulating nucleic acid enzymes.
- Raghav R. Poudyal
- , Rebecca M. Guth-Metzler
- & Philip C. Bevilacqua
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Article
| Open AccessTranslation of non-standard codon nucleotides reveals minimal requirements for codon-anticodon interactions
The recognition of the mRNA codon by the tRNA anticodon is crucial for protein synthesis. Here the authors introduce non-standard nucleotides in bacterial and eukaryotic mRNA to reveal the minimal hydrogen bond requirement of codon-anticodon interaction for efficient and accurate translation.
- Thomas Philipp Hoernes
- , Klaus Faserl
- & Matthias David Erlacher
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Article
| Open AccessCrystal structure of an RNA-cleaving DNAzyme
RNA-cleaving DNA enzymes are catalytic DNA that can cleave RNA in a sequence-specific manner. Here, the authors report three crystal structures of the 8–17 DNAzyme that include the pre-catalytic state of the RNA cleavage reaction, providing insight into the catalytic mechanism and may guide the rational design of DNAzymes.
- Hehua Liu
- , Xiang Yu
- & Jianhua Gan
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Article
| Open AccessTwister ribozymes as highly versatile expression platforms for artificial riboswitches
Twister ribozymes are small endonucleolytic RNA motifs. Here the authors develop twister ribozymes into RNA logic gates and cross-species synthetic genetic regulators.
- Michele Felletti
- , Julia Stifel
- & Jörg S. Hartig
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| Open AccessRibozyme-enhanced single-stranded Ago2-processed interfering RNA triggers efficient gene silencing with fewer off-target effects
Short hairpin RNAs are widely used to produce small interfering RNAs (siRNAs) for gene silencing. Here, the authors show that an alternative siRNA precursor in the presence of a self-cleaving ribozyme has enhanced silencing activity and reduced off-target effects, providing a potential RNAi tool.
- Renfu Shang
- , Fengjuan Zhang
- & Ligang Wu
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Article |
In-line alignment and Mg2+ coordination at the cleavage site of the env22 twister ribozyme
Twisters ribozymes are a recently discovered class of non-coding, site-specific self-cleaving RNAs. Here Ren et al. describe a crystal structure of the env22twister ribozyme, propose an ion coordination and catalytic mechanism, and contrast their findings with those of two recently reported twister structures.
- Aiming Ren
- , Marija Košutić
- & Dinshaw J. Patel
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Article |
Ice as a protocellular medium for RNA replication
A crucial transition in the origin of life was the emergence of self-replicating RNA and its compartmentalization within protocellular structures. Here it is shown that the physicochemical properties of ice, a simple medium widespread on a temperate early earth, could have mediated this transition.
- James Attwater
- , Aniela Wochner
- & Philipp Holliger