Cellular landscape illustrating ribosome regulation by decapping enzymes in the nucleolus, highlighting PNRC1's role as a control mechanism.

Can Decapping Enzymes Stop Cancer? New Insights into Ribosome Regulation

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Mira Elwood in Science & Nature December 2025 • 5 min read.

"A recent study reveals how PNRC1, a key mRNA decapping coactivator, acts as a tumor suppressor by precisely controlling ribosome production."


Ribosomes are essential for protein synthesis, coordinating the formation of peptide bonds with tRNA decoding of mRNA. Disruptions in protein synthesis are a recognized hallmark of cancer, making the regulation of this process a critical area of study. The rate-limiting step for most mRNA transcripts involves cap-dependent translation initiation, where eukaryotic initiation factors (eIFs) recruit ribosomes using the 5' terminal m7G cap structure. Elevated levels of initiation factors are linked to increased translation of oncogenic mRNAs and cellular transformation, highlighting the importance of controlled translation initiation.

Cells employ several mechanisms to regulate translation, including the phosphorylation of eIFs and the removal of the 5' cap structure by decapping enzymes. This decapping process is a definitive form of translational repression, leading to the degradation of RNA by 5'-3' exonucleases. Increased ribosome production is also associated with cancer, prompting questions about how oncogenes manipulate ribosome biogenesis to transform cells. Recent research sheds light on the role of proline-rich nuclear receptor coactivator 1 (PNRC1) as a tumor suppressor, limiting ribosome production by directing the Dcp1/Dcp2 decapping complex to selectively decapitate U3 and U8 small nucleolar RNAs (snoRNAs), thereby inhibiting ribosome biogenesis.

A study by Gaviraghi et al. (2018) reveals that PNRC1 functions as a gatekeeper, restraining oncogenic potential by influencing rRNA processing and ribosome biogenesis. This unexpected finding was derived from mining The Cancer Genome Atlas (TCGA) and RNA-Seq data, identifying genes with specific copy number alterations and low expression patterns. The analysis highlighted PNRC1, a nucleolar factor with previously uncharacterized functions.

PNRC1's Role in Ribosome Biogenesis: A New Target for Cancer Therapy?

Cellular landscape illustrating ribosome regulation by decapping enzymes in the nucleolus, highlighting PNRC1's role as a control mechanism.

The nucleolus is the primary site for ribosomal RNA (rRNA) transcription and processing. Here, the 47S pre-rRNA is transcribed by RNA Polymerase I and processed into mature 5.8S, 18S, and 28S rRNA isoforms. This processing is guided by ribonucleoprotein assemblies directed by small nucleolar RNAs (snoRNAs). Gaviraghi and colleagues demonstrated that PNRC1 localizes to rRNA processing sites in the nucleolus, reducing the accumulation of mature 18S and 28S rRNA—critical components of ribosomal subunits.

Further investigation using immunoprecipitation coupled with mass spectrometry (IP-MS) revealed that PNRC1 interacts with the Dcp1/Dcp2 mRNA decapping complex. This complex, typically involved in mRNA decay, consists of the catalytic subunit Dcp2, the activator Dcp1, and various pathway-specific coactivators. Like its paralog PNRC2, PNRC1 contains short linear motifs that enhance the mRNA decapping activity of Dcp1/Dcp2. While mRNA decapping often occurs in cytoplasmic mRNA processing bodies (P-bodies), PNRC1 expression causes Dcp1/Dcp2 to relocalize to the nucleolus, dispersing P-bodies in the process.

  • PNRC1 as a Tumor Suppressor: PNRC1 is typically not expressed in patient cancer cells compared to normal controls. Its expression is mutually exclusive with proliferation in primary cells and various cell lines.
  • Inhibition of Oncogenic Effects: Ectopic expression of PNRC1 reduces proliferation induced by RAS and MYC, and it diminishes the ability of these oncogenes to promote focus formation on soft agar.
  • Decapping of snoRNAs: PNRC1 promotes the decapping of specific snoRNAs (U3 and U8), which are unique as they are transcribed by RNA Polymerase II and contain a m7G cap structure. This decapping inhibits ribosome biogenesis by affecting the processing of pre-rRNA.
This specificity is critical because U3 snoRNP facilitates the cleavage of external and internal spacer sequences (ETS1 and ITS1) during 47S pre-rRNA processing. By increasing the ratio of 47S pre-rRNA to 28S product, PNRC1 influences the decapping of U3 snoRNA, confirmed by decreased U3 snoRNA presence when using anti-cap beads and increased ligation efficiency when PNRC1 is expressed.

Future Directions: Decapping, RNA Metabolism, and Cancer

This research opens avenues for exploring the relationship between decapping, RNA metabolism, and cancer. For instance, the loss of the decapping enzyme Nudt16 has been linked to C-MYC activation in leukemia. Nudt16, like PNRC1, can decap U8 snoRNA and is found in both the nucleolus and cytoplasm. Further studies could explore whether Nudt16 acts as a tumor suppressor and if it targets the same oncogenes as PNRC1.

Additionally, while PNRC1-mediated decapping does not alter the steady-state levels of U3 or U8 snoRNAs, the decapped RNAs may be protected from degradation by exoribonucleases like Xrn2. This raises questions about whether PNRC1 misregulates other aspects of snoRNP biology, such as localization, or affects other targets within cells.

It's also worth noting that the yeast decapping coactivator Edc2 shares Dcp1-binding and Dcp2-activating motifs with PNRC1 and is found in the nucleolus, suggesting that Dcp1/Dcp2-mediated decapping in ribosome biogenesis and cell proliferation is a conserved process warranting further investigation.

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This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.15252/embj.2018100801, Alternate LINK

Title: Decapping Enzymes Stop “Cancer” Ribosomes In Their Tracks

Subject: General Immunology and Microbiology

Journal: The EMBO Journal

Publisher: EMBO

Authors: Jeffrey S Mugridge, John D Gross

Published: 2018-11-19

Everything You Need To Know

1

What is PNRC1, and how does it work to fight cancer?

PNRC1 (proline-rich nuclear receptor coactivator 1) is a key mRNA decapping coactivator that functions as a tumor suppressor. It achieves this by regulating ribosome biogenesis. It directs the Dcp1/Dcp2 complex to decapping snoRNAs (U3 and U8). The expression of PNRC1 is typically not seen in cancer cells compared to normal cells, and its presence is linked to reduced proliferation and the inhibition of oncogenic effects.

2

Why is the regulation of ribosome biogenesis important in the context of cancer?

Ribosomes are essential for protein synthesis, and disruptions in this process are a hallmark of cancer. The Dcp1/Dcp2 complex is a decapping enzyme involved in mRNA decay, and PNRC1 directs it to specifically decap snoRNAs. By targeting these snoRNAs, PNRC1 influences the processing of pre-rRNA, leading to the inhibition of ribosome biogenesis. This targeted decapping is critical because it reduces the production of ribosomes, which are often overproduced in cancer cells, supporting tumor growth.

3

How does PNRC1 influence the function of the Dcp1/Dcp2 decapping complex?

The Dcp1/Dcp2 complex, which is composed of the catalytic subunit Dcp2, the activator Dcp1, and various coactivators, is typically found in cytoplasmic mRNA processing bodies (P-bodies), where it removes the 5' cap structure from mRNA. PNRC1's interaction with this complex causes it to relocate to the nucleolus, the site of ribosome biogenesis. In the nucleolus, the complex targets specific snoRNAs (U3 and U8) instead of mRNA, thereby inhibiting ribosome biogenesis and suppressing tumor growth.

4

What is the role of snoRNAs in the process PNRC1 uses to fight cancer?

PNRC1 influences the processing of 47S pre-rRNA, which is a precursor to the mature ribosomal RNA components (5.8S, 18S, and 28S rRNA). The snoRNAs U3 and U8 play roles in this processing. PNRC1's decapping of U3 snoRNA specifically, impacts the cleavage of sequences during 47S pre-rRNA processing. By increasing the ratio of 47S pre-rRNA to 28S product, PNRC1 ultimately reduces the production of mature ribosomal subunits, thereby inhibiting ribosome biogenesis and tumor growth.

5

What is the significance of decapping in cancer, and what are the implications of this research?

Decapping, the removal of the 5' cap structure from RNA, is a significant regulatory mechanism in cells. In this context, the decapping activity of the Dcp1/Dcp2 complex, directed by PNRC1, specifically targets snoRNAs U3 and U8, which affects ribosome biogenesis. The research suggests that manipulating decapping enzymes, like PNRC1, could be a potential therapeutic strategy against cancer. The study also highlights the potential of other decapping enzymes, such as Nudt16, as additional targets for cancer therapy.

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