N6-methyladenosine reader YTHDF3-mediated CEBPA translation maintains genomic stability and stem cell function to prevent liver injury
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.The N6-methyladenine reader YTHDF3 protects against liver injury by regulating CEBPA translation and maintaining genomic stability. Its absence exacerbates liver damage and DNA instability.
Area Of Science
- Hepatology
- Molecular Biology
- Epigenetics
Background
- Liver injury poses significant health risks.
- The role of N6-methyladenine (m6A) reader YTHDF3 in liver injury is not well understood.
Purpose Of The Study
- To investigate the precise mechanisms of YTHDF3 in liver injury.
- To elucidate the regulatory role of YTHDF3 in liver cell function and genomic stability.
Main Methods
- Single-cell RNA sequencing
- Organoid culture
- Ythdf3 knockout mouse model
- Carbon tetrachloride (CCl4)-induced liver injury model
Main Results
- Ythdf3 knockout exacerbated CCl4-induced liver injury, reducing functional hepatocytes and liver stem cells.
- m6A dysregulation mediated by Mettl14 and YTHDF3 induced DNA damage.
- YTHDF3 regulates CCAAT/enhancer-binding protein-alpha (CEBPA) translation in an m6A-dependent manner.
- Ythdf3 deficiency inhibited CEBPA translation, leading to reduced PARP1 and PRDX2 expression, promoting DNA damage and genomic instability.
Conclusions
- The m6A/YTHDF3/CEBPA axis is crucial for maintaining cell fates and genomic stability in the liver.
- Targeting YTHDF3 and CEBPA presents potential therapeutic strategies for liver injury-related diseases.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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...
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.