Evidence map›Paper›PMID 41418754›Full record

ArticleMolecular cell2025

Defective RNA processing and ELOA-mediated transcriptional elongation in reversible cellular senescence suggest aging by transcription.

Saeid Parast, Simai Wang, Marta Iwanaszko, Yue He, Deniz G Olgun, Sarah Gold, Jacob M Zeidner, Yuki Aoi, Benjamin C Howard, William R Thakur and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Saeid ParastSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Simai WangGladstone Institute for Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Marta IwanaszkoSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Yue HeSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Deniz G OlgunGladstone Institute for Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Sarah GoldSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Jacob M ZeidnerSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Yuki AoiSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Benjamin C HowardSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
William R ThakurSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Vijay RamaniGladstone Institute for Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Ali ShilatifardSimpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: ash@northwestern.edu.

Funding

Mutations of Chromatin and its Modifying Machineries in MalignanciesR35CA197569 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Ali Shilatifard · 2015 to 2026
$10.7M
SINGLE-CELL CHEMICAL TRANSCRIPTOMIC DISSECTION OF AN ESSENTIAL TRANSCRIPTION FACTOR NETWORKDP2HG012442 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RAMANI, VIJAY · 2021 to 2024
$2.6M
Epigenetics, Metabolism and CancerT32CA281953 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Ali Shilatifard · 2023 to 2026
$1.2M
Computational Approaches for Studying Transcription Elongation Control in CancerR50CA265372 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Marta Iwanaszko · 2022 to 2026
$722k
NCI NIH HHS R35 CA197569NCI NIH HHS R50 CA265372NCI NIH HHS T32 CA281953NHGRI NIH HHS DP2 HG012442
6 · The paper itself

Abstract

We previously established distinct roles for the transcriptional elongation factors PAF1, negative elongation factor (NELF), SPT4/5, and SPT6 using auxin-inducible degron systems in human cell lines. Here, we integrate long- and short-read RNA-seq data from these degron lines to quantify transcript isoform usage at single-molecule resolution, identifying elongation factor-specific RNA processing regulons, including a cellular senescence-enriched regulon impacted by NELF and SPT6. Long-term NELF or SPT6 depletion causes reversible growth arrest following early upregulation of senescence-associated genes. Our genetic suppressor screens implicate the elongation factor Elongin A (ELOA) in these effects. ELOA knockout suppresses the progression of RNA polymerase II (RNAPII) past transcription end sites (TESs) at NELF depletion-induced genes. Acute depletion of TES-proximal ELOA causes a loss of RNAPII processivity at the 3' end of genes. ELOA loss also confers a growth advantage to aging primary human fibroblasts. These findings establish NELF/ELOA-dependent mechanisms regulating transcriptional elongation and RNA processing and link them to senescence and aging.

Indexed as

Cellular SenescenceElonginRNA Processing, Post-TranscriptionalTranscriptional Elongation FactorsTranscription Elongation, GeneticTranscription, GeneticFibroblastsHumansNuclear ProteinsRNA Polymerase IITranscription FactorsElonginnegative elongation factorNuclear ProteinsRNA Polymerase IITranscriptional Elongation FactorsTranscription Factorsagingcellular senescencegene expressionmRNA processingtranscriptiontranscriptional elongation

Identifiers

PMID41418754
PMCPMC13214445

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.