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Published on: August 6, 2019
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.
Abstract:
Cancer cells frequently upregulate ribosome production to support tumorigenesis. While small nucleolar RNAs (snoRNAs) are critical for ribosome biogenesis, the roles of other classes of noncoding RNAs in this process remain largely unknown. Here, we performed CRISPR interference (CRISPRi) screens to identify essential long noncoding RNAs (lncRNAs) in renal cell carcinoma (RCC) cells. This revealed that an alternatively spliced isoform of lncRNA colorectal neoplasia differentially expressed (CRNDE) containing an ultraconserved element (UCE), referred to as CRNDEUCE, is required for RCC cell proliferation. CRNDEUCE localizes to the nucleolus and promotes 60S ribosomal subunit biogenesis. The UCE of CRNDE functions as an unprocessed C/D box snoRNA that directly interacts with ribosomal RNA precursors. This facilitates delivery of eukaryotic initiation factor 6 (eIF6), a key 60S biogenesis factor, which binds to CRNDEUCE through a sequence element adjacent to the UCE. These findings highlight the functional versatility of snoRNA sequences and expand the known mechanisms through which noncoding RNAs orchestrate ribosome biogenesis.
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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