SnoRNA U50 levels are regulated by cell proliferation and rRNA transcription

Annalisa Pacilli1, Claudio Ceccarelli, Davide Treré

  • 1Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Sant'Orsola-Malpighi University Hospital, Bologna 40138, Italy. annalisa.pacilli@gmail.com

Insights

Small nucleolar RNA U50 (U50) downregulation in colon cancer correlates with reduced ribosomal RNA methylation and impaired ribosome function. This suggests U50’s role in regulating cell proliferation and its potential as a tumor suppressor.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • Post-transcriptional modifications of ribosomal RNA (rRNA) are crucial for ribosomal function and implicated in cancer development.
  • Small nucleolar RNA U50 (U50) targets C2848 methylation in 28S rRNA and has been proposed as a tumor suppressor in various cancers.

Purpose of the Study:

  • To investigate the role of U50 in colon cancer and its impact on cellular proliferation and ribosome function.
  • To explore the mechanisms underlying U50 downregulation in cancer.

Main Methods:

  • Analysis of U50 levels in colon cancer cell lines and tumors.
  • Investigating U50 expression and C2848 methylation in phytohemagglutinin-stimulated lymphocytes.
  • Assessing U50 stability and consumption under conditions of blocked ribosome biogenesis.
  • Evaluating the effect of U50 modulation on IRES-mediated translation.

Main Results:

  • U50 was found to be downregulated in colon cancer cell lines and tumors.
  • Decreased U50 levels in lymphocytes correlated with reduced C2848 methylation and were linked to altered U50 stability and increased consumption.
  • Blockade of ribosome biogenesis led to an initial decrease in U50, followed by stabilization.
  • U50 modulation was shown to affect ribosome efficiency in IRES-mediated translation.

Conclusions:

  • The study links U50 to cellular proliferation rates and ribosome biogenesis.
  • Findings suggest that reduced U50 levels contribute to altered ribosome function and may explain its downregulation in cancers.
  • U50's role in regulating ribosome efficiency highlights its potential significance in cancer development.

Related Concept Videos

Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
The Nucleolus02:55

The Nucleolus

The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...