{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:21:18Z","timestamp":1788297678648,"version":"build-2803163510"},"reference-count":109,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["5R01AI119131"],"award-info":[{"award-number":["5R01AI119131"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"award":["5R01AI119131"],"award-info":[{"award-number":["5R01AI119131"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    CC-chemokine ligand 2 (CCL2) is involved in the pathogenesis of several diseases associated with monocyte\/macrophage recruitment, such as HIV-associated neurocognitive disorder (HAND), tuberculosis, and atherosclerosis. The rs1024611 (alleles: A&gt;G; G is the risk allele) polymorphism in the\n                    <jats:italic>CCL2 cis<\/jats:italic>\n                    -regulatory region is associated with increased CCL2 expression in vitro and ex vivo, leukocyte mobilization in vivo, and deleterious disease outcomes. However, the molecular basis for the rs1024611-associated differential CCL2 expression remains poorly characterized. It is conceivable that genetic variant(s) in linkage disequilibrium (LD) with rs1024611 could mediate such effects. Previously, we used rs13900 (alleles: C&gt;T) in the\n                    <jats:italic>CCL2<\/jats:italic>\n                    3\u2032untranslated region (3\u2032 UTR) that is in perfect LD with rs1024611 to demonstrate allelic expression imbalance (AEI) of\n                    <jats:italic>CCL2<\/jats:italic>\n                    in heterozygous individuals. Here, we tested the hypothesis that the rs13900 could modulate\n                    <jats:italic>CCL2<\/jats:italic>\n                    expression by altering mRNA turnover and\/or translatability. The rs13900 T allele conferred greater stability to the\n                    <jats:italic>CCL2<\/jats:italic>\n                    transcript when compared to the rs13900 C allele. The rs13900 T allele also had increased binding to Human Antigen R (HuR), an RNA-binding protein, in vitro and ex vivo. The rs13900 alleles imparted differential activity to reporter vectors and influenced the translatability of the reporter transcript. We further demonstrated the role of HuR in mediating allele-specific effects on CCL2 expression in overexpression and silencing studies. Our studies suggest that the differential interactions of HuR with rs13900 could modulate CCL2 expression and could in part explain the interindividual differences in CCL2-mediated disease susceptibility.\n                  <\/jats:p>","DOI":"10.7554\/elife.93108","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T14:25:35Z","timestamp":1706019935000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.93108","source":"Crossref","is-referenced-by-count":1,"title":["The RNA-binding protein HuR modulates the expression of the disease-linked CCL2 rs1024611G-rs13900T haplotype"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1381-3856","authenticated-orcid":true,"given":"Feroz","family":"Akhtar","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0084njv03","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Health and Behavioral Sciences, Texas A&M University-San Antonio","place":["San 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