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Updated: Jan 8, 2026

Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Defective RNA processing and ELOA-mediated transcriptional elongation in reversible cellular senescence suggest aging
Saeid Parast1, Simai Wang2, Marta Iwanaszko1
1Simpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
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.
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