Evidence map›Paper›PMID 42520802›Full record

ArticleCell2026

Coordinated RNA- and protein-templated synthesis of double-stranded DNA by a dual reverse transcriptase immune system.

Megan Wang, Kanta Yoneyama, Rimantė Žedaveinytė, Junichiro Ishikawa, Stephen Tang, Hoang C Le, Tanner Wiegand, Josephine L Ramirez, Naoto Nagahata, Yanzhe Ma and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Megan WangDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Kanta YoneyamaStructural Biology Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
Rimantė ŽedaveinytėDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Junichiro IshikawaDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Stephen TangDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Hoang C LeDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Tanner WiegandDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
Josephine L RamirezDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Naoto NagahataDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Yanzhe MaDepartment of Biological Sciences, Columbia University, New York, NY 10027, USA.
Dennis J ZhangDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Erick HelmecziMetabolomics Core, Shared Research Resources, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Mirela BerisaMetabolomics Core, Shared Research Resources, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Marko JovanovicDepartment of Biological Sciences, Columbia University, New York, NY 10027, USA.
Masahiro HiraizumiDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Keitaro YamashitaStructural Biology Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
Hiroshi NishimasuStructural Biology Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Inamori Research Institute for Science, 620 Suiginya-cho, Shimogyo-ku, Kyoto 600-8411, Japan. Electronic address: nisimasu@g.ecc.u-tokyo.ac.jp.
Samuel H SternbergDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA. Electronic address: shsternberg@gmail.com.

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Medical Scientist Training ProgramT32GM145440 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI STEVEN L REINER · 2022 to 2026
$7.3M
How dynamic molecular interactions of RNA Binding Proteins drive post-transcriptional gene expression changesR35GM152258 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Marko Jovanovic · 2024 to 2026
$1.6M
Mechanisms of reverse transcriptase mediated phage resistance in EnterobacteriaceaeF30AI183830 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Stephen Tang · 2024 to 2026
$158k
NHGRI NIH HHS RM1 HG009490NIAID NIH HHS F30 AI183830NIGMS NIH HHS R35 GM152258NIGMS NIH HHS T32 GM145440
6 · The paper itself

Abstract

Defense-associated reverse transcriptase (DRT) systems mediate antiviral immunity through distinct modes of cDNA synthesis: class 1 DRTs catalyze untemplated synthesis, whereas class 2 DRTs polymerize non-coding RNA-templated products. However, how these distinct modes drive defense remains unclear. Here, we report that DRT3 immunity arises when class 1 and class 2 RT activities cooperate to produce self-complementary double-stranded DNA (dsDNA). DRT3a uses a 5'-ACACAC-3' RNA template to synthesize poly-(dTdG) repeats, whereas DRT3b synthesizes poly-(dCdA) repeats without any nucleic acid template. Cryo-electron microscopy reveals that DRT3b forms a hexamer and uses active-site-adjacent residues as deoxyadenosine and deoxycytidine gates to enforce alternating nucleotide addition, representing a unique example of amino-acid-templated DNA polymerization. DRT3 is toxic in cells lacking RecBCD, implicating host recombination machinery in limiting dsDNA accumulation, and the phage-encoded RecBCD inhibitor Gam triggers DRT3-mediated abortive infection. These findings reveal how two polymerases with distinct templating strategies generate complementary DNA for antiviral defense.

Indexed as

DNARNA-Directed DNA PolymeraseCryoelectron MicroscopyEscherichia coliRNADNARNARNA-Directed DNA Polymeraseabortive infectionbacterial immunitydefense-associated reverse transcriptaseDRT3non-coding RNAphage defenseprotein-primed cDNA synthesisprotein-templated cDNA synthesisretroelementreverse transcriptase

Identifiers

PMID42520802
PMCPMC13419432

What OpenQuestion holds

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Registered trials

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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.