Evidence map›Paper›PMID 34498588›Full record

ArticleeLife2021

Witnessing the structural evolution of an RNA enzyme.

Xavier Portillo, Yu-Ting Huang, Ronald R Breaker, David P Horning, Gerald F Joyce

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. A GTP synthase ribozyme with increased GTP turnover.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Bioengineering hybrid artificial life.Frontiers in bioinformatics · 2025
    Review
  7. RNA World with Inhibitors.Entropy (Basel, Switzerland) · 2024
    Article
  8. Directionality theory and the origin of life.Royal Society open science · 2024
    Article
  9. RNA life on the edge of catastrophe.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. RNA-catalyzed evolution of catalytic RNA.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  11. Cryo-EM structure and functional landscape of an RNA polymerase ribozyme.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Review
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Xavier PortilloDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States.ORCID 0000-0003-1225-1133
Yu-Ting HuangThe Salk Institute, La Jolla, United States.
Ronald R BreakerDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, United States.ORCID 0000-0002-2165-536X
David P HorningThe Salk Institute, La Jolla, United States.ORCID 0000-0003-3357-6092
Gerald F JoyceThe Salk Institute, La Jolla, United States.ORCID 0000-0003-0603-2874
Salk Institute for Biological Studies · USHoward Hughes Medical Institute · USYale University · US

Funding

X-RAY ANALYSIS OF PROTEIN STRUCTURE AND FUNCTIONP01GM022778 · NIGMS · YALE UNIVERSITY · PI BREAKER, RONALD R · 1985 to 2019
$26.1M
Howard Hughes Medical InstituteNIGMS NIH HHS P01 GM022778
6 · The paper itself

Abstract

An RNA polymerase ribozyme that has been the subject of extensive directed evolution efforts has attained the ability to synthesize complex functional RNAs, including a full-length copy of its own evolutionary ancestor. During the course of evolution, the catalytic core of the ribozyme has undergone a major structural rearrangement, resulting in a novel tertiary structural element that lies in close proximity to the active site. Through a combination of site-directed mutagenesis, structural probing, and deep sequencing analysis, the trajectory of evolution was seen to involve the progressive stabilization of the new structure, which provides the basis for improved catalytic activity of the ribozyme. Multiple paths to the new structure were explored by the evolving population, converging upon a common solution. Tertiary structural remodeling of RNA is known to occur in nature, as evidenced by the phylogenetic analysis of extant organisms, but this type of structural innovation had not previously been observed in an experimental setting. Despite prior speculation that the catalytic core of the ribozyme had become trapped in a narrow local fitness optimum, the evolving population has broken through to a new fitness locale, raising the possibility that further improvement of polymerase activity may be achievable.

Indexed as

Directed Molecular EvolutionEvolution, MolecularCatalysisCatalytic DomainDNA-Directed RNA PolymerasesMutationNucleic Acid ConformationPhylogenyProtein ConformationRNA, CatalyticStructure-Activity RelationshipDNA-Directed RNA PolymerasesRNA, Catalyticbiochemistrychemical biologymolecular evolutionnoneribozymeRNA polymerase

Identifiers

PMID34498588
PMCPMC8460264
OpenAlexW3197736901

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.