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Updated: Jul 15, 2026

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
RNA polymerase III transcription is repressed in response to the tumour suppressor ARF
Jennifer P Morton1, Theodoros Kantidakis, Robert J White
1Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, UK.
Abstract:
The tumour suppressor protein ARF provides a defence mechanism against hyperproliferative stresses that can result from the aberrant activation of oncogenes. Accordingly, ARF is silenced or deleted in many human cancers. Activation of ARF can arrest growth and cell cycle progression, or trigger apoptosis. A principle mediator of these effects is p53, which ARF stabilizes by binding and inhibiting MDM2. However, ARF has additional targets and remains able to block growth in the absence of p53, albeit less efficiently. For example, ARF can suppress rRNA production in a p53-independent manner. We have found that the synthesis of tRNA by RNA polymerase III is also inhibited in response to ARF. However, in contrast to its effects on rRNA synthesis, ARF is unable to inhibit tRNA gene transcription when p53 is ablated. These results add to the growing list of cellular changes that can be triggered by ARF induction.
Insights
The tumor suppressor ARF inhibits tRNA synthesis, a process dependent on the p53 protein. This reveals a new p53-dependent mechanism by which ARF controls cell growth and proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- The tumor suppressor protein ARF defends against hyperproliferation caused by oncogene activation.
- ARF is often silenced or deleted in human cancers.
- ARF activation can halt cell growth and cycle progression or induce apoptosis, often by stabilizing p53 via MDM2 inhibition.
Purpose of the Study:
- To investigate the role of ARF in regulating tRNA synthesis.
- To determine if ARF's inhibition of tRNA synthesis is p53-dependent.
Main Methods:
- Investigated the effect of ARF on tRNA synthesis.
- Examined ARF's impact on tRNA gene transcription in the presence and absence of p53.
Main Results:
- ARF was found to inhibit the synthesis of tRNA.
- Unlike its p53-independent suppression of rRNA synthesis, ARF's inhibition of tRNA gene transcription requires the presence of p53.
Conclusions:
- ARF regulates tRNA synthesis through a p53-dependent pathway.
- This adds tRNA synthesis inhibition to the list of cellular changes induced by ARF.
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