Evidence map›Paper›PMID 41993428›Full record

ArticlebioRxiv : the preprint server for biology2026

Screening metatranscriptomes for ultrastable RNA secondary structures reveals hidden bacteriophages and novel capsid nanomaterials.

Daniel A Villarreal, Nino Makasarashvili, Aaryan Kapoor, Max Root, Matthew Campbell, Skylar Gibson, Conor Schiveley, Amineh Rastandeh, Sherry Baker, Sundharraman Subramanian and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 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

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

17 authors.

Daniel A VillarrealDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.
Nino MakasarashviliDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.
Aaryan KapoorDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.
Max RootDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.
Matthew CampbellDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.
Skylar GibsonDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.
Conor SchiveleyDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.
Amineh RastandehDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.
Sherry BakerDepartment of Biology, San Diego State University, San Diego, CA, USA.
Sundharraman SubramanianDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Uri NeriDepartment of Energy Joint Genome Institute, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Carolyn E MillsDepartment of Bioengineering, University of California, Santa Barbara, Santa Barbara, CA, USA.
Katelyn McNairComputational Science Research Center, San Diego State University, San Diego, CA, USA.
Anca M SegallDepartment of Biology, San Diego State University, San Diego, CA, USA.
Uri GophnaThe Shmunis School of Biomedicine and Cancer Research, Tel Aviv University, Tel Aviv, Israel.
Kristin N ParentDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Rees F GarmannDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, CA, USA.

Funding

Bacteriophage interactions with enteric pathogens-the essential role of inner membrane protein YajCR35GM140803 · NIGMS · MICHIGAN STATE UNIVERSITY · PI Kristin N Parent · 2021 to 2026
$2.5M
Direct measurements of RNA virus nucleocapsid self-assembly and disassemblyR35GM157105 · NIGMS · SAN DIEGO STATE UNIVERSITY · PI Rees F Garmann · 2025 to 2026
$746k
NIGMS NIH HHS R35 GM140803NIGMS NIH HHS R35 GM157105
6 · The paper itself

Abstract

Metatranscriptomics has transformed our view of RNA bacteriophage diversity, revealing vast numbers of single-stranded RNA (ssRNA) phages whose protein capsids can be engineered for biotechnology applications. However, many ssRNA phages remain hidden from current detection methods, which require protein-level similarity to known phages. Here we show that RNA structure provides an additional signal for the detection of ssRNA phages in metatranscriptomes, including hidden phages missed by prior protein-based methods. By computationally folding each contig and screening for exceptionally stable RNA secondary structures, we find evidence of thousands of previously unrecognized phages encoding novel coat proteins. We express a library of 12,000 such coat proteins in E. coli and find that most assemble into nuclease-resistant capsids. We determine the 3D structure of one such capsid by cryo-electron microscopy and demonstrate that it can be disassembled and reassembled in vitro to package heterologous RNA-a key step toward repurposing these particles as RNA delivery vehicles. We compile the newly discovered ssRNA phages with previously known ones into a database that contains sequence and structural information for over 460,000 unique RNA molecules and over 100,000 distinct coat proteins, providing a comprehensive resource for microbiology and nanomaterials research.

Indexed as

BiochemistryBiological Sciencescapsid nanomaterialsmetatranscriptomicsRNA structuressRNA bacteriophageviral discovery

Identifiers

PMID41993428
PMCPMC13082091

What OpenQuestion holds

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LicenceCC BY-NC
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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.