Evidence map›Paper›PMID 38567721›Full record

ArticleNucleic acids research2024

The effect of pseudoknot base pairing on cotranscriptional structural switching of the fluoride riboswitch.

Laura M Hertz, Elise N White, Konstantin Kuznedelov, Luyi Cheng, Angela M Yu, Rivaan Kakkaramadam, Konstantin Severinov, Alan Chen, Julius B Lucks

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Laura M HertzInterdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60208, USA.
Elise N WhiteDepartment of Chemistry and the RNA Institute, University at Albany, Albany, NY 12222, USA.
Konstantin KuznedelovWaksman Institute of Microbiology, Rutgers University, Piscataway, NJ 08854, USA.
Luyi ChengInterdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60208, USA.
Angela M YuDepartment of Electrical and Computer Engineering, University of Washington, Seattle, WA 98195, USA.
Rivaan KakkaramadamDepartment of Chemistry and the RNA Institute, University at Albany, Albany, NY 12222, USA.
Konstantin SeverinovWaksman Institute of Microbiology, Rutgers University, Piscataway, NJ 08854, USA.ORCID 0000-0001-9706-450X
Alan ChenDepartment of Chemistry and the RNA Institute, University at Albany, Albany, NY 12222, USA.ORCID 0000-0001-8246-2935
Julius B LucksInterdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60208, USA.ORCID 0000-0002-0619-6505
Northwestern University · USUniversity at Albany, State University of New York · USRutgers, The State University of New Jersey · USUniversity of Washington · US

Funding

Developing Capacity to Evaluate Training Programs via Development of Human, Institutional and Social CapitalT32GM008449 · NIGMS · NORTHWESTERN UNIVERSITY · PI LEONARD, JOSHUA NATHANIEL · 1993 to 2023
$7.8M
Tri-Institutional Training Program in Computational Biology & MedicineT32GM083937 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHRISTINI, DAVID J. · 2009 to 2018
$3.1M
Thermodynamically Calibrated RNA Simulations to Decode Mechanisms of RNAMolecular RecognitionR35GM133469 · NIGMS · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI Alan Austin Chen · 2019 to 2026
$2.9M
NIGMS NIH HHS R01 GM10407NIGMS NIH HHS R35 GM133469NIGMS NIH HHS T32 GM008449NIGMS NIH HHS T32 GM083937NIH HHS T32GM008449
6 · The paper itself

Abstract

A central question in biology is how RNA sequence changes influence dynamic conformational changes during cotranscriptional folding. Here we investigated this question through the study of transcriptional fluoride riboswitches, non-coding RNAs that sense the fluoride anion through the coordinated folding and rearrangement of a pseudoknotted aptamer domain and a downstream intrinsic terminator expression platform. Using a combination of Escherichia coli RNA polymerase in vitro transcription and cellular gene expression assays, we characterized the function of mesophilic and thermophilic fluoride riboswitch variants. We showed that only variants containing the mesophilic pseudoknot function at 37°C. We next systematically varied the pseudoknot sequence and found that a single wobble base pair is critical for function. Characterizing thermophilic variants at 65°C through Thermus aquaticus RNA polymerase in vitro transcription showed the importance of this wobble pair for function even at elevated temperatures. Finally, we performed all-atom molecular dynamics simulations which supported the experimental findings, visualized the RNA structure switching process, and provided insight into the important role of magnesium ions. Together these studies provide deeper insights into the role of riboswitch sequence in influencing folding and function that will be important for understanding of RNA-based gene regulation and for synthetic biology applications.

Indexed as

Base PairingEscherichia coliFluoridesNucleic Acid ConformationRiboswitchTranscription, GeneticBase SequenceDNA-Directed RNA PolymerasesMagnesiumMolecular Dynamics SimulationRNA, BacterialRNA FoldingThermusDNA-Directed RNA PolymerasesFluoridesMagnesiumRiboswitchRNA, Bacterial

Identifiers

PMID38567721
PMCPMC11077080
OpenAlexW4393856472

What OpenQuestion holds

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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.