Related Experiment Video
Updated: Jul 8, 2026
10:50
Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
Neurochondrin promotes U5 snRNP maturation by regulating AAR2 release from PRPF8
Tingrong Ren1, Wanru Huang1, Gaigai Wei1
1Fudan University Pudong Medical Center and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Nucleic Acids Research
|July 7, 2026
Summary
Neurochondrin (NCDN) is crucial for assembling the U5 small nuclear ribonucleoprotein (snRNP), a key spliceosome component. Its deficiency impacts tumor growth and survival, suggesting NCDN as a therapeutic target in glioma.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The spliceosome, a complex machinery, orchestrates pre-mRNA splicing.
- The biogenesis of small nuclear ribonucleoproteins (snRNPs), essential spliceosome components, is not fully understood.
- Dysregulation of spliceosome function is linked to alternative splicing defects and cancer.
Purpose of the Study:
- To identify novel regulators of U5 snRNP biogenesis.
- To investigate the role of neurochondrin (NCDN) in spliceosome assembly and function.
- To explore the therapeutic potential of targeting NCDN in glioma.
Main Methods:
- Co-immunoprecipitation to identify protein interactions.
- Western blotting to assess protein levels.
- RNA sequencing to analyze transcriptome-wide changes.
- Cell proliferation and apoptosis assays.
Main Results:
- Neurochondrin (NCDN) was identified as a critical regulator of U5 snRNP biogenesis.
- NCDN associates with the PRPF8-AAR2-EFTUD2 complex and is essential for U5 snRNP maturation.
- Loss of NCDN leads to accumulation of assembly intermediates and reduced mature U5 snRNP levels.
- NCDN deficiency suppresses tumor cell proliferation and induces apoptosis.
- High NCDN expression correlates with poor survival in glioblastoma patients.
- NCDN depletion causes widespread alternative splicing defects and gene expression changes.
Conclusions:
- NCDN is an essential factor for U5 snRNP assembly and spliceosome function.
- NCDN plays a significant role in regulating tumor cell growth and survival.
- NCDN represents a potential therapeutic target for glioma with elevated expression.
Related Concept Videos
01:45Regulation 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...
02:41Chromatin 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...
The chromatin structure, especially...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
01:37The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
01:34Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
01:42Nuclear Export
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...