{
  "abstract": "Circular RNAs (circRNAs) are covalently closed transcripts that lack a 5' cap, consequently their translation depends on cap-independent initiation, in most cases through Internal Ribosome Entry Sites (IRESs). Whereas IRES-mediated translation has been studied almost exclusively in cis, the use of IRES-containing circRNAs to activate translation of an independent mRNA in trans has only recently begun to be explored. Here, we characterize SynFarsa, a synthetic circRNA-derived IRES-like element that promotes cap-lindependent translation in mouse and human cells. We engineered SynFarsa into a trans-acting regulator by fusing it to a short antisense sequence complementary to a selected region of a target mRNA. This reproduces the architecture of a circular SINEUP, in which IRES activity promotes translation in trans of a transcript recognized through antisense complementarity. Directing this construct to the hsp90 3'UTR increased HSP90 protein levels approximately 1.6-lfold without altering hsp90 mRNA abundance, whereas the hsp70 3'UTR and the 5'UTRs of both transcripts were not permissive, indicating that activity depends strongly on target site selection. In a FUSP525L neuroblastoma model of Amyotrophic Lateral Sclerosis, this increase in HSP90 was accompanied by a reduction in the number and size of cytoplasmic FUS aggregates. SynFarsa thus provides a circRNA-derived effector domain for targeted translational upregulation of an endogenous protein.",
  "abstract_shown": true,
  "affiliations": [
    "Italian Institute of Technology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "G. Aoun"
    },
    {
      "name": "A. Vandelli"
    },
    {
      "name": "R. Delli Ponti"
    },
    {
      "name": "S. Gustincich"
    },
    {
      "name": "E. Bechara"
    },
    {
      "name": "L. Broglia"
    },
    {
      "affs": [
        0
      ],
      "name": "G. G. Tartaglia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ccs4m4h2y70h4.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.05.756760",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756760v1.full",
  "id": "ccs4m4h2y70h4",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756760v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ],
    [
      "openalex",
      "1312|Circular RNAs in diseases"
    ]
  ],
  "openalex": "W7220747123",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756760v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ccs4m4h2y70h4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:13Z",
      "native_id": "10.64898/2026.10.05.756760",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756760v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Circular RNAs in diseases",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A circRNA-derived IRES-like element enables programmable translational activation of the endogenous chaperone HSP90",
  "title_text": "A circRNA-derived IRES-like element enables programmable translational activation of the endogenous chaperone HSP90",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:13Z",
  "url": "https://research.draconitic.com/paper/ccs4m4h2y70h4",
  "venue": "bioRxiv",
  "versions": []
}