{
  "abstract": "Translation initiation defines the protein output of the transcriptome, but its physiological dynamics in cells and tissues remain incompletely characterized. Here we develop TISCA2, an inhibitor-free method that captures eIF5B-associated initiating ribosomes to map translation initiation sites genome-wide. By directly identifying start sites rather than inferring translation from elongating-ribosome periodicity, TISCA2 improves the detection of short and overlapping translons. Translation of a subset of TISCA2-identified translons is supported by N-terminal proteomics and HLA-I immunopeptidomics. The arsenite-induced integrated stress response broadly redistributes start-site usage, reducing upstream initiation in favor of downstream initiation. TISCA2 further reveals tissue-specific initiation landscapes in vivo, with increased detection of downstream candidate start sites in the testis. Finally, we develop IncepTIS, a sequence-based deep learning model that predicts position-resolved and condition-dependent initiation landscapes. IncepTIS-guided optimization generates de novo mRNA 5' leaders with stress-responsive initiation patterns. Together, TISCA2 and IncepTIS provide an experimental and computational framework for mapping, predicting and engineering translation initiation in mammalian cells and tissues.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602 Japan.; Research Institute of Environmental Medicine, Nagoya Univ"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "name": "K. Ichihara"
    },
    {
      "name": "T. Shiraishi"
    },
    {
      "name": "H. Morita"
    },
    {
      "name": "C. Shiraishi"
    },
    {
      "name": "M. Hirata"
    },
    {
      "name": "N. Yamashiki"
    },
    {
      "name": "S. Setsu"
    },
    {
      "name": "K. Tsuboyama"
    },
    {
      "name": "A. Hatano"
    },
    {
      "name": "S. Tokita"
    },
    {
      "name": "E. Mishiro-Sato"
    },
    {
      "name": "A. Sakamoto"
    },
    {
      "name": "T. Ito"
    },
    {
      "name": "K. Abe"
    },
    {
      "name": "M. Seki"
    },
    {
      "name": "Y. Suzuki"
    },
    {
      "name": "M. Ajiro"
    },
    {
      "name": "A. Yoshimi"
    },
    {
      "name": "T. Kanaseki"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Matsumoto"
    },
    {
      "name": "S. Adachi"
    },
    {
      "name": "P. V. Baranov"
    },
    {
      "name": "T. Shimamura"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Matsumoto"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c8ja3jr827xrb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.03.763266",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763266v1.full",
  "id": "c8ja3jr827xrb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763266v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763266v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c8ja3jr827xrb.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:42Z",
      "native_id": "10.64898/2026.11.03.763266",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.03.763266v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Physiological mapping and prediction reveal stress-responsive translation initiation landscapes",
  "title_text": "Physiological mapping and prediction reveal stress-responsive translation initiation landscapes",
  "type": "preprint",
  "updated_at": "2026-11-07T00:20:54Z",
  "url": "https://research.draconitic.com/paper/c8ja3jr827xrb",
  "venue": "bioRxiv",
  "versions": []
}