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The regulation of RNA polymerase II levels

Bautu, Theodora (2025) MOBN03 20242
Degree Projects in Molecular Biology
Popular Abstract
The regulation of RNAPII levels - The RNA-polymerase II (RNAPII) controls transcription. But who controls the RNAPII?

Every cell in our body depends on a process called transcription, which turns genetic instructions into messages (mRNA) that can be used to make proteins. This essential job is carried out by a molecular machine known as RNA polymerase II (RNAPII). While many studies have investigated how RNAPII regulates transcription, not much is known about how RNAPII itself is regulated.

My thesis investigates a newly proposed feedback loop: when levels of a key RNAPII component, RPB1, fall, the cell reacts by boosting production of the POLR2A gene, which encodes RPB1, as well as the POLR2A mRNA stability. It’s as if the cell... (More)
The regulation of RNAPII levels - The RNA-polymerase II (RNAPII) controls transcription. But who controls the RNAPII?

Every cell in our body depends on a process called transcription, which turns genetic instructions into messages (mRNA) that can be used to make proteins. This essential job is carried out by a molecular machine known as RNA polymerase II (RNAPII). While many studies have investigated how RNAPII regulates transcription, not much is known about how RNAPII itself is regulated.

My thesis investigates a newly proposed feedback loop: when levels of a key RNAPII component, RPB1, fall, the cell reacts by boosting production of the POLR2A gene, which encodes RPB1, as well as the POLR2A mRNA stability. It’s as if the cell senses what is missing and tries to restore the balance by making more. I wanted to understand how this self-regulating system works.

To do this, I tested whether certain genetic regions of POLR2A – called untranslated regions (UTRs) and promoter – helped regulate how much POLR2A mRNA the cell makes, or how stable the mRNA is. Using a reporter assay and RNA quantification, I discovered that the UTRs do not play a role in regulating the POLR2A mRNA abundance. However, I found that a small 128bp core promoter region in the POLR2A gene is sufficient for enabling POLR2A transcription. When I removed one highly conserved part of this sequence, the cell’s POLR2A mRNA levels dropped by half.

I also explored which proteins might help regulate the POLR2A mRNA stability. Using a method that tags molecules in close proximity, I identified several proteins – like YBX1, NCBP2 and PARN – that may help stabilize POLR2A mRNA, especially when RPB1 is missing.
These insights into how cells fine-tune RNAPII production may help us understand how gene expression becomes disrupted in diseases like cancer, or in response to environmental stress like UV radiation. Moreover, my research sheds light on how the cell keeps one of its most powerful tools – RNAPII – under tight control.







Master’s Degree Project in Molecular Biology, 60cr, 2025
Department of Biology, Lund University
The thesis was carried out at the University of Copenhagen, in the Svejstrup Lab, at ICMM, CGEN. (Less)
Please use this url to cite or link to this publication:
author
Bautu, Theodora
supervisor
organization
course
MOBN03 20242
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9214996
date added to LUP
2025-11-06 13:29:58
date last changed
2025-11-06 13:29:58
@misc{9214996,
  author       = {{Bautu, Theodora}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{The regulation of RNA polymerase II levels}},
  year         = {{2025}},
}