{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:56:52Z","timestamp":1792173412045,"version":"4.4.0"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"42","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:p>\n                    Genomic DNA can adopt noncanonical secondary structures, such as G-quadruplexes (G4s), which serve as critical regulatory elements beyond the traditional double helix. Whether promoter G4s also participate in controlling innate immune signaling and host\u2013pathogen interactions, however, remains unknown in arthropods. In this study, we identify a G4 structure within the promoter of the\n                    <jats:italic toggle=\"yes\">NEMO<\/jats:italic>\n                    (NF-\u03baB essential modulator) gene in the deer tick\n                    <jats:italic toggle=\"yes\">Ixodes scapularis<\/jats:italic>\n                    . Using a combination of circular dichroism, isothermal difference spectra, and fluorescence-based assays, we demonstrate that this sequence forms a stable, parallel G4 topology in vitro and in vivo. Functional characterization via luciferase reporter assays reveals that this G4 scaffold is essential for proper\n                    <jats:italic toggle=\"yes\">NEMO<\/jats:italic>\n                    transcriptional output. Importantly, disruption of the G4 structure significantly reduces\n                    <jats:italic toggle=\"yes\">NEMO<\/jats:italic>\n                    expression and increases the burden of the Lyme disease spirochete\n                    <jats:italic toggle=\"yes\">Borrelia burgdorferi<\/jats:italic>\n                    . Genome-wide expression profiling further reveals that perturbation of the\n                    <jats:italic toggle=\"yes\">NEMO<\/jats:italic>\n                    G4 produces transcriptional changes that overlap with those observed following\n                    <jats:italic toggle=\"yes\">NEMO<\/jats:italic>\n                    silencing. These shared transcriptional responses are enriched for immune-associated genes and ribonucleoprotein-related pathways. We further identify the heterogeneous nuclear ribonucleoprotein Hrb27C as a structural binding protein that specifically recognizes the\n                    <jats:italic toggle=\"yes\">NEMO<\/jats:italic>\n                    G4 through its RNA recognition motif domains and facilitates\n                    <jats:italic toggle=\"yes\">NEMO<\/jats:italic>\n                    expression. Collectively, our findings establish promoter G4 architecture as an important regulatory layer in tick immunity, linking DNA topology to pathogen proliferation and providing a structural framework for understanding host\u2013pathogen dynamics in disease vectors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2612352123","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:39:04Z","timestamp":1792172344000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["A promoter G-quadruplex recruits Hrb27C to regulate NEMO and immune defense against Lyme disease pathogens in the deer tick"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2744-730X","authenticated-orcid":false,"given":"Bo","family":"Lyu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Plant Science and Technology, University of Missouri","place":["Columbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyuan","family":"Gao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Plant Science and Technology, University of Missouri","place":["Columbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah M.","family":"Anderson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathobiology & Biomedical Sciences, University of Missouri","place":["Columbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stanley","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01na82s61","id-type":"ROR","asserted-by":"publisher"}],"name":"Biological Control of Insect Research Laboratory, United States Department of Agriculture-Agricultural Research Station","place":["Columbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9682-1775","authenticated-orcid":false,"given":"Qisheng","family":"Song","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ymw8z06","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Plant Science and Technology, University of Missouri","place":["Columbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3296"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-0131-2"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trechm.2019.07.002"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27134165"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf042"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.91985.3"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01643-4"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.4c00574"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-025-03654-y"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02324-z"},{"key":"e_1_3_4_11_2","first-page":"11746","article-title":"G-quadruplex structures trigger RNA phase separation","volume":"47","author":"Zhang Y.","year":"2019","unstructured":"Y. Zhang , G-quadruplex structures trigger RNA phase separation. 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