Related Experiment Video
Updated: Feb 18, 2026
10:05
Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
6.9K
Nucleolin phosphorylation regulates PARN deadenylase activity during cellular stress response
Xiaokan Zhang1, Shu Xiao2, Rachele Dolce Rameau2
1a Chemistry Department , Hunter College , New York , NY , USA.
RNA Biology
|November 24, 2017
Summary
Nucleolin phosphorylation is essential for regulating gene expression by activating the deadenylase PARN during cellular stress. This process controls mRNA stability and protein levels, impacting cell proliferation and stress responses.
Area of Science:
- Molecular Biology
- Gene Regulation
- Cellular Stress Response
Background:
- Nucleolin (NCL) is a key RNA-binding protein involved in gene expression.
- NCL's role in mRNA stability, translation, and deadenylation is known, but the impact of its phosphorylation remains unclear.
- Previous work showed NCL phosphorylation is vital for cell cycle progression.
Purpose of the Study:
- To investigate the mechanism of NCL phosphorylation in regulating gene expression.
- To identify the deadenylase involved in NCL-mediated mRNA deadenylation.
- To elucidate how NCL phosphorylation affects protein-protein and protein-RNA interactions during stress.
Main Methods:
- Site-directed mutagenesis to create phosphorylation-deficient NCL mutants.
- Biochemical assays to assess deadenylase activity (PARN).
- Co-immunoprecipitation to study protein-protein interactions.
- RNA immunoprecipitation to analyze protein-RNA interactions.
Main Results:
- NCL phosphorylation at CK2 sites is crucial for activating poly(A)-specific ribonuclease (PARN) deadenylase activity under oncogenic and UV stress.
- NCL directly interacts with PARN, and this interaction is modulated by NCL phosphorylation status.
- Phosphorylation-deficient NCL favors interactions with p53 and HuR under stress, while NCL-WT interacts with PARN to downregulate TP53 and BCL2 mRNA levels.
Conclusions:
- NCL phosphorylation provides specificity to protein-protein and protein-RNA interactions.
- NCL phosphorylation regulates PARN deadenylase activity, thereby controlling gene expression during cellular stress.
- This study reveals a novel mechanism for stress-induced gene regulation mediated by NCL phosphorylation.
Related Concept Videos
02:36DNA Damage Can Stall the Cell Cycle
3.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.2K
02:36DNA Damage can Stall the Cell Cycle
10.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.2K
02:04Covalently Linked Protein Regulators
9.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.7K
01:45Regulation of Nuclear Protein Sorting
3.4K
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...
3.4K
02:55The Nucleolus
10.5K
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,...
10.5K
01:02Phosphorylation
54.5K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
54.5K