---
title: "Shared helical core topology in arenavirus intergenic RNAs"
id: "biorxiv-3-comparative-analysis-identifies-a-shared-topological-organisation-among"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-3-comparative-analysis-identifies-a-shared-topological-organisation-among"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.22.760956v1?rss=1"
published_at: "2026-10-24T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Shared helical core topology in arenavirus intergenic RNAs
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-3-comparative-analysis-identifies-a-shared-topological-organisation-among
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.22.760956v1?rss=1)
- **Published At:** 2026-10-24T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators used **cryo-OrbiSIMS** guided RNA structure determination combined with graph theory to compare fifty-eight intergenic regions across diverse arenaviruses. - The study team observed a recurring topological organisation: a highly connected helical core anchors each IGR despite divergent global folds. - Quantitative centrality analyses indicated that peripheral stem-loops occupy low-centrality positions and vary across phylogenetic classes. - Data indicated that topological features were not captured by sequence identity or by global RNA-structure similarity, suggesting topology can be orthogonal to primary sequence conservation. - Functional probing focused on the S-segment IGR from **Golden Gate virus**; the cohort showed selective association of its peripheral elements with interferon-induced and antiviral RNA-binding proteins when assayed in human cells infected with recombinant **Lymphocytic Choriomeningitis virus**. - Authors noted a model in which a topologically central helical organisation may relate to conserved regulatory capacity, while structurally variable peripheral elements contribute to lineage- or segment-specific host-factor interactions. - The article is a preprint and has not been peer reviewed. The source did not report detailed experimental parameters for all assays in the abstract (for example, stepwise protocols, sample preparation parameters, or quantitative thresholds used in centrality metrics).
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Alex Childs 1 University of Nottingham; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Alex%2BChilds%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Childs%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAlex%2BChilds%2B) Dinh Thien Kim Ly 1 University of Nottingham; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Dinh%2BThien%2BKim%2BLy%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Ly%20DT&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ADinh%2BThien%2BKim%2BLy%2B) Tycho Marinus 2 Rijksuniversiteit Groningen; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Tycho%2BMarinus%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Marinus%20T&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ATycho%2BMarinus%2B) Rahul Arvind Bhosale 1 University of Nottingham; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Rahul%2BArvind%2BBhosale%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bhosale%20RA&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ARahul%2BArvind%2BBhosale%2B) * [ORCID record for Rahul Arvind Bhosale](http://orcid.org/0000-0001-6515-4922 "Open in new tab") Janet M Daly 1 University of Nottingham; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Janet%2BM%2BDaly%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Daly%20JM&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJanet%2BM%2BDaly%2B) * [ORCID record for Janet M Daly](http://orcid.org/0000-0002-1912-4500 "Open in new tab") Katarzyna Tych 2 Rijksuniversiteit Groningen; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Katarzyna%2BTych%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Tych%20K&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AKatarzyna%2BTych%2B) * [ORCID record for Katarzyna Tych](http://orcid.org/0000-0001-9091-0507 "Open in new tab") Toshana L Foster 1 University of Nottingham; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Toshana%2BL%2BFoster%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Foster%20TL&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AToshana%2BL%2BFoster%2B) * [ORCID record for Toshana L Foster](http://orcid.org/0000-0001-7752-8987 "Open in new tab") Aditi Narendra Borkar 3 University of Liverpool * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Aditi%2BNarendra%2BBorkar%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Borkar%20AN&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAditi%2BNarendra%2BBorkar%2B) * [ORCID record for Aditi Narendra Borkar](http://orcid.org/0000-0001-9278-1438 "Open in new tab") * For correspondence: a.n.borkar@liverpool.ac.uk * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.22.760956v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5901242/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.22.760956v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5901242/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.22.760956v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5901242/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.22.760956v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5901242/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Biological function is often inferred from sequence conservation or structural similarity. However, many viral RNAs maintain regulatory functions despite extensive diversification of both sequence and structures. Using arenavirus intergenic regions (IGRs) as a model system, we investigated what level of RNA organization remains conserved when these conventional sequence-structure-function relationships break down. Combining cryogenic OrbiSIMS guided RNA structure determination with graph theory-based analysis of fifty-eight IGRs across phylogenetically diverse arenaviruses, we discovered that IGR topology, defined by the connectivity and relative integration of individual stem-loop elements, is consistently arranged around a highly connected helical core that persists across divergent IGR folds. Quantitative centrality analyses further revealed that topologically peripheral stem-loops are comparatively sparse and variable across the phylogenetic classes. Investigation of the functional consequence of the peripheral elements in Golden Gate virus (a reptile arenavirus) S-IGR revealed selective association with interferon-induced and antiviral RNA-binding proteins in human host cells infected with recombinant Lymphocytic Choriomeningitis virus (a distantly related human arenavirus). Taken together, these findings identify graph-defined topology as a recurrent organisational feature among divergent arenavirus IGRs that is not captured by sequence identity or global RNA-structure similarity. The data are consistent with a model in which a topologically central helical organisation may be associated with conserved regulatory capacity, whereas structurally variable peripheral elements may contribute to lineage- or segment-specific host-factor interaction profiles. ### Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC-ND 4.0 International license](http://creativecommons.org/licenses/by-nc-nd/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.22.760956v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/24/2026.10.22.760956.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Comparative analysis identifies a shared topological organisation among divergent intergenic RNAs Alex Childs, Dinh Thien Kim Ly, Tycho Marinus, Rahul Arvind Bhosale, Janet M Daly, Katarzyna Tych, Toshana L Foster, Aditi Narendra Borkar bioRxiv 2026.10.22.760956; doi: https://doi.org/10.64898/2026.10.22.760956 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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