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Agata Stepien @agatakstepien.bsky.social · 5h

5. Many thanks to @stoplab.bsky.social, @dpulimamidi.bsky.social, Martyna Plens-Gałąska, Maxime Lalonde, @mgkopczynska.bsky.social, Klaudia Ostatek, Mariia Kapeliukha, Shazia Irshad, Hiroshi Kimura, @michal-gdula.bsky.social , and Stephan Hamperl for a great collaboration on this project.

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Agata Stepien @agatakstepien.bsky.social · 5h

4. And here's the exciting connection: Shorter distance between RNA cleavage and RNAPII terminal pausing is associated with higher gene expression and greater dependence on #PCF11 and #CPSF73. We see this relationship in pancreatic cancer cells too! Could this reveal a new vulnerability in cancer?

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Agata Stepien @agatakstepien.bsky.social · 5h

3. The story changes again in metastatic cells! Compared to primary tumor cells, cleavage shifts to more proximal polyadenylation sites, while RNAPII pauses more distally. Another striking example of how changes in RNA processing and transcription termination can become uncoupled.

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Agata Stepien @agatakstepien.bsky.social · 5h

2. Compared to normal colon cells, primary tumor cells tend to cleave RNA at more distal sites – but RNAPII terminal pausing shifts proximally. Two processes thought to be tightly linked move in opposite directions. The result? A shorter distance between RNA cleavage and transcription termination.

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Agata Stepien @agatakstepien.bsky.social · 5h

1. Colorectal cancer cells are highly dependent on two key RNA processing factors: #PCF11 and #CPSF73. But here’s the surprise: primary tumor cells depend on them much more than metastatic cells. Why?

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Agata Stepien @agatakstepien.bsky.social · 5h

Two steps in gene expression that should move together… don’t. In our new paper we show that pre-mRNA cleavage and RNA polymerase II (RNAPII) termination shift in opposite directions – with a surprising link to gene expression and cancer cell vulnerability. Read more here: tinyurl.com/3pkeuctp

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Reposted by Agata Stepien

Kinga Kamieniarz-Gdula @stoplab.bsky.social · 01/07/2026

There is more to transcriptional readthrough than meets the eye, and it could even provide a therapeutic opportunity in cancer. Check out our new perspective, inspired by recent work from Neugebauer and Grzechnik labs! #RNABiology #RNASky #Epigenetics

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Agata Stepien @agatakstepien.bsky.social · 01/07/2026

Studying gene ends is becoming even more fascinating! Curious why? Read our News & Views "Transcriptional readthrough progresses from incidental byproduct to therapeutic opportunity" inspired by the recent publication by Podszywałow-Bartnicka and @karlaneugebauer.bsky.social @natsmb.nature.com

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Agata Stepien @agatakstepien.bsky.social · 04/12/2025

5. Many thanks to @stoplab.bsky.social, @dpulimamidi.bsky.social , Martyna Plens-Galaska, Maxime Lalonde, @mgkopczynska.bsky.social, Shazia Irshad, Hiroshi Kimura, @michal-gdula.bsky.social, and Stephan Hamperl for a great collaboration on this project. 6/6

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Agata Stepien @agatakstepien.bsky.social · 04/12/2025

4. Shortening of the distance between pre-mRNA cleavage and RNAPII terminal pausing is associated with higher gene expression❗️ Shortened spacing = higher expression BUT also higher addiction to PCF11 and CPSF73. 5/6

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Agata Stepien @agatakstepien.bsky.social · 04/12/2025

3. Comparing metastatic with primary tumor CRC cells, we again observed that changes in PAS selection and RNAPII terminal pausing are not unidirectional (proximal PAS & distal RNAPII terminal pausing). 4/6

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Agata Stepien @agatakstepien.bsky.social · 04/12/2025

2. In our model, primary tumor cells display a tendency for selection of distal polyadenylation site (PAS), and at the same time, proximal (!) shift of RNAPII terminal pausing as compared to normal colon cells (= #uncoupling & shortened spacing between PAS and termination). 3/6

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Agata Stepien @agatakstepien.bsky.social · 04/12/2025

1. Colorectal cancer (CRC) cell clonogenicity critically depends on #PCF11 and #CPSF73, with primary tumor cells showing much higher addiction to those factors than metastatic cells. Why??? 🤔2/6

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Agata Stepien @agatakstepien.bsky.social · 04/12/2025

Did you know that changes in pre-mRNA 3' cleavage and RNAPII termination can go in different directions? Even more, the spacing between these two events is linked to the gene expression level❗️Check out our latest pre-print to learn more tiny.cc/330w001 1/6

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