Related Experiment Video
Updated: Aug 12, 2025
10:05
Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
6.5K
Long Non-Coding RNA Generated from CDKN1A Gene by Alternative Polyadenylation Regulates p21 Expression during DNA
Biorxiv : the Preprint Server for Biology
|January 30, 2023
Summary
A new long non-coding RNA, SPUD, is induced by DNA damage to regulate p21 protein levels. This discovery reveals a novel post-transcriptional mechanism controlling cell-cycle progression and DNA damage response.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Alternative Polyadenylation (APA) dynamically regulates gene expression.
- Widespread APA occurs in introns during the DNA damage response (DDR).
Approach:
- Identified a DNA damage-activated APA event in the first intron of CDKN1A, generating a novel long non-coding RNA (lncRNA) named SPUD.
- Investigated SPUD's localization, abundance, induction factors (p53, HuR, CTCF), and functional impact on p21.
- Analyzed SPUD's interaction with p21 translational regulators (calreticulin, CUGBP1) during DDR.
Key Points:
- SPUD is a novel ALE-containing lncRNA induced by DNA damage via p53.
- SPUD selectively increases p21 protein levels, impacting cell-cycle and viability.
- SPUD modulates p21 translational regulators in a DDR-dependent manner.
Conclusions:
- SPUD represents a new post-transcriptional regulatory mechanism controlling p21 expression.
- This lncRNA-mediated control is crucial for DDR progression and cell-cycle regulation.
Related Concept Videos
01:23Negative Regulator Molecules
35.5K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.5K
02:37DNA Damage can Stall the Cell Cycle
9.2K
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...
9.2K
02:34Inhibition of Cdk Activity
4.9K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
02:39lncRNA - Long Non-coding RNAs
8.7K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.7K
02:23Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
02:39Positive Regulator Molecules
5.6K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.6K