An ultraconserved snoRNA-like element in long noncoding RNA CRNDE promotes ribosome biogenesis and cell proliferation

Jong-Sun Lee1, Tu Dan2, He Zhang3

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Molecular Cell
|April 4, 2025
PubMed

Insights

A novel long noncoding RNA (lncRNA), CRNDEUCE, is essential for renal cell carcinoma (RCC) cell proliferation by promoting 60S ribosome biogenesis. This RNA acts as a small nucleolar RNA (snoRNA) to facilitate ribosome production in cancer cells.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • RNA Biology

Background:

  • Cancer cells require increased ribosome production for rapid proliferation.
  • Small nucleolar RNAs (snoRNAs) are known regulators of ribosome biogenesis.
  • The role of other noncoding RNAs in ribosome production is largely unexplored.

Purpose of the Study:

  • To identify essential long noncoding RNAs (lncRNAs) involved in renal cell carcinoma (RCC) cell proliferation.
  • To elucidate the function of a specific lncRNA, CRNDEUCE, in ribosome biogenesis.

Main Methods:

  • CRISPR interference (CRISPRi) screening in RCC cells.
  • Localization studies of CRNDEUCE in the nucleolus.
  • Investigation of CRNDEUCE interaction with ribosomal RNA (rRNA) and eukaryotic initiation factor 6 (eIF6).

Main Results:

  • CRNDEUCE, an alternatively spliced lncRNA, is crucial for RCC cell proliferation.
  • CRNDEUCE promotes 60S ribosomal subunit biogenesis.
  • The ultraconserved element (UCE) within CRNDE functions as a snoRNA, interacting with rRNA and facilitating eIF6 binding.

Conclusions:

  • The lncRNA CRNDEUCE plays a critical role in supporting cancer cell growth through ribosome biogenesis.
  • This study reveals the functional versatility of snoRNA sequences within lncRNAs.
  • Noncoding RNAs are key orchestrators of ribosome biogenesis, offering potential therapeutic targets in cancer.

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