{
  "abstract": "Synonymous codons occur at unequal rates in the coding genome, with those represented least often termed 'rare.' Rare codon-enriched genes typically exhibit poor expression due to reduced transcription, mRNA stability, export, and translation. However, there are an increasing number of examples whereby rare codon-enriched genes are paradoxically highly expressed, suggestive of mechanisms to overcome the poor expression imposed by rare codons. To identify codon-dependent modifiers, we screen a targeted sgRNA library for genes that, when inactivated, increase the expression of rare versus common codon-enriched fluorescent reporters. This identifies the PAXT connection, a nuclear complex that targets transcripts to the exosome for degradation. Targeted loss of a PAXT component leads to a small but preferential increase in mRNA levels and stability and a more pronounced increase in protein expression of rare compared to common codon-enriched reporters. Transcriptomics coupled to proteomics further reveals that this leads to a preferential increase in the expression of endogenous proteins encoded by poorly expressed and long mRNAs specifically enriched in rare codons. Thus, we identify the PAXT connection as a genetic suppressor of poorly expressed genes enriched in rare codons.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC, USA.",
    "Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.",
    "Department of Cell Biology, Duke University Medical Center, Durham, NC, USA.",
    "Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC, USA. count004@mc.duke.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Taylor Niehoff",
      "orcid": "0000-0002-0506-6012"
    },
    {
      "affs": [
        0
      ],
      "name": "Jackson Peterson"
    },
    {
      "affs": [
        0
      ],
      "name": "Siqi Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Sijin Chen",
      "orcid": "0009-0006-3511-9919"
    },
    {
      "affs": [
        2
      ],
      "name": "Christopher V Nicchitta",
      "orcid": "0000-0001-7889-1155"
    },
    {
      "affs": [
        1
      ],
      "name": "Alain Laederach"
    },
    {
      "affs": [
        3
      ],
      "name": "Christopher M Counter",
      "orcid": "0000-0003-0748-3079"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2b8nhbrsg6yzd.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77792-7",
  "fulltext_url": "https://europepmc.org/articles/PMC13680609",
  "id": "2b8nhbrsg6yzd",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897178",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|RNA and protein synthesis mechanisms"
    ]
  ],
  "openalex": "W7213463865",
  "pdf_url": "https://europepmc.org/articles/PMC13680609?pdf=render",
  "pmcid": "PMC13680609",
  "pmid": "42897178",
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2b8nhbrsg6yzd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42897178",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897178"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA and protein synthesis mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "The PAXT connection is a modifier of rare codon-enriched protein expression.",
  "title_text": "The PAXT connection is a modifier of rare codon-enriched protein expression.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:41Z",
  "url": "https://research.draconitic.com/paper/2b8nhbrsg6yzd",
  "venue": "Nature communications",
  "versions": []
}