Evidence map›Paper›PMID 40071935›Full record

ArticleNucleic acids research2025

Structural investigation of an RNA device that regulates PD-1 expression in mammalian cells.

Jason R Stagno, Justin C Deme, Vibha Dwivedi, Yun-Tzai Lee, Hyun Kyung Lee, Ping Yu, Szu-Yun Chen, Lixin Fan, Maximilia F S Degenhardt, Raj Chari and 3 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

13 authors.

Jason R StagnoProtein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Justin C DemeMolecular Basis of Disease Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Vibha DwivediProtein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Yun-Tzai LeeProtein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Hyun Kyung LeeProtein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Ping YuProtein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Szu-Yun ChenProtein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Lixin FanBasic Science Program, Frederick National Laboratory for Cancer Research, SAXS Core Facility of the National Cancer Institute, Frederick, MD, 21702, United States.
Maximilia F S DegenhardtProtein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Raj ChariGenome Modification Core, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.ORCID 0000-0002-2216-313X
Howard A YoungCellular and Molecular Immunology Section, Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Susan M LeaMolecular Basis of Disease Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.
Yun-Xing WangProtein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, United States.ORCID 0000-0002-2175-0148

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
X-ray Scattering Technology CoreP30GM133893 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI Sean McSweeney · 2019 to 2026
$38.6M
A Simultaneous SAXS/WAXS Detector System for Solving Biological StructuresS10OD012331 · OD · STATE UNIVERSITY NEW YORK STONY BROOK · PI ALLAIRE, MARC · 2012 to 2012
$1.1M
CCR NIH HHS HHSN261200800001CDepartment of Energy Basic Energy Sciences Program DE-SC0012704Department of Energy's Office of Biological and Environmental Research KP1605010HHS HHS75N91019D00024NCI NIH HHSNIGMS NIH HHS P30 GM133893NIGMS NIH HHS P30GM133893NIH HHS 75N91019D00024NIH HHS HHSN261200800001ENIH HHS S10 OD012331
6 · The paper itself

Abstract

Synthetic RNA devices are engineered to control gene expression and offer great potential in both biotechnology and clinical applications. Here, we present multidisciplinary structural and biochemical data for a tetracycline (Tc)-responsive RNA device (D43) in both ligand-free and bound states, providing a structure-dynamical basis for signal transmission. Activation of self-cleavage is achieved via ligand-induced conformational and dynamical changes that stabilize the elongated bridging helix harboring the communication module, which drives proper coordination of the catalytic residues. We then show the utility of CRISPR-integrated D43 in EL4 lymphocytes to regulate programmed cell death protein 1 (PD-1), a key receptor of immune checkpoints. Treatment of these cells with Tc showed a dose-dependent reduction in PD-1 by immunostaining and a decrease in messenger RNA levels by quantitative PCR as compared with wild type. PD-1 expression was recoverable upon removal of Tc. These results provide mechanistic insight into RNA devices with potential for cancer immunotherapy or other applications.

Indexed as

Gene Expression RegulationProgrammed Cell Death 1 ReceptorRNAAnimalsCRISPR-Cas SystemsHumansLymphocytesMiceNucleic Acid ConformationTetracyclinePDCD1 protein, humanProgrammed Cell Death 1 ReceptorRNATetracycline

Identifiers

PMID40071935
PMCPMC11897892

What OpenQuestion holds

Textmetadata
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.