Evidence map›Paper›PMID 30007279›Full record

ArticleNucleic acids research2018

Template-assisted synthesis of adenine-mutagenized cDNA by a retroelement protein complex.

Sumit Handa, Yong Jiang, Sijia Tao, Robert Foreman, Raymond F Schinazi, Jeff F Miller, Partho Ghosh

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.3field-weighted citation impact, top 10% 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

20 citing papers in PubMed, 37 citations in OpenAlex.

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  19. Beyond cells - The virome in the human holobiont.Microbial cell (Graz, Austria) · 2019
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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

7 authors at 3 institutions in 1 country.

Sumit HandaDepartment of Chemistry & Biochemistry, University of California, San Diego, CA 92093, USA.
Yong JiangCenter for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Sijia TaoCenter for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Robert ForemanDepartment of Chemistry & Biochemistry, University of California, San Diego, CA 92093, USA.
Raymond F SchinaziCenter for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Jeff F MillerDepartments of Microbiology, Immunology, and Molecular Genetics, Molecular Biology Institute, and California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Partho GhoshDepartment of Chemistry & Biochemistry, University of California, San Diego, CA 92093, USA.
Emory University · USUniversity of California San Diego · USUniversity of California, Los Angeles · US

Funding

Diversity-Generation and Variable Protein Displays in Pathogens and PhageR01AI096838 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GHOSH, PARTHO, MILLER, JEFFERY F. · 2012 to 2016
$2.7M
NIAID NIH HHS R01 AI096838
6 · The paper itself

Abstract

Diversity-generating retroelements (DGRs) create unparalleled levels of protein sequence variation through mutagenic retrohoming. Sequence information is transferred from an invariant template region (TR), through an RNA intermediate, to a protein-coding variable region. Selective infidelity at adenines during transfer is a hallmark of DGRs from disparate bacteria, archaea, and microbial viruses. We recapitulated selective infidelity in vitro for the prototypical Bordetella bacteriophage DGR. A complex of the DGR reverse transcriptase bRT and pentameric accessory variability determinant (Avd) protein along with DGR RNA were necessary and sufficient for synthesis of template-primed, covalently linked RNA-cDNA molecules, as observed in vivo. We identified RNA-cDNA molecules to be branched and most plausibly linked through 2'-5' phosphodiester bonds. Adenine-mutagenesis was intrinsic to the bRT-Avd complex, which displayed unprecedented promiscuity while reverse transcribing adenines of either DGR or non-DGR RNA templates. In contrast, bRT-Avd processivity was strictly dependent on the template, occurring only for the DGR RNA. This restriction was mainly due to a noncoding segment downstream of TR, which specifically bound Avd and created a privileged site for processive polymerization. Restriction to DGR RNA may protect the host genome from damage. These results define the early steps in a novel pathway for massive sequence diversification.

Indexed as

Templates, GeneticAdenineBacteriophagesBordetellaDNA, ComplementaryGenetic VariationMutagenesis, InsertionalMutagenesis, Site-DirectedMutagensRetroelementsRNA-Directed DNA PolymeraseAdenineDNA, ComplementaryMutagensRetroelementsRNA-Directed DNA Polymerase

Identifiers

PMID30007279
PMCPMC6182149
OpenAlexW2951988846

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.