Related Experiment Video
Updated: May 12, 2026
08:40
Dot Blot Assay for Detecting Global N6-Methyladenosine RNA Modification Levels
Published on: February 6, 2026
METTL3-Mediated m6A Modification Promotes the Stability of PLCζ mRNA in Sperm
Chao Yang1, Longling Han1, Wenting Xu1
1Department of Reproductive Medicine, The Maternal and Child Health Hospital of Changde City, Changde, Hunan Province, People's Republic of China.
Molecular Reproduction and Development
|May 11, 2026
Summary
METTL3 enhances sperm function by stabilizing PLCζ mRNA via N6-methyladenosine modification. This process is crucial for maintaining fertilization capacity and prostate secretory homeostasis, addressing male infertility concerns.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Epigenetics
Background:
- Male infertility is a significant global health issue, often linked to sperm dysfunction.
- Phospholipase C zeta (PLCζ) is vital for oocyte activation and fertilization; its reduced expression correlates with fertilization failure.
- N6-methyladenosine (m6A) modification plays a role in gene expression, but its specific function in sperm and relation to PLCζ is unclear.
Purpose of the Study:
- To investigate the role of METTL3-mediated m6A modification in regulating PLCζ expression and sperm function.
- To elucidate the mechanism by which METTL3 influences PLCζ mRNA stability and its impact on male fertility.
Main Methods:
- Quantification of PLCζ, METTL3, METTL14, and WTAP mRNA and protein levels in human sperm.
- Assessment of sperm morphology, zinc/citrate content, and global m6A levels in patients with low fertilization rates (LFR).
- RNA immunoprecipitation (RIP) to analyze METTL3 binding to PLCζ mRNA and transcription inhibition assays to determine mRNA stability.
Main Results:
- PLCζ expression was downregulated in LFR patients, correlating with lower zinc/citrate content and reduced global m6A levels.
- METTL3 inhibition in mouse sperm decreased PLCζ expression and impaired prostate secretory function.
- METTL3 inhibition destabilized PLCζ mRNA by reducing its m6A modification, highlighting a direct mechanistic link.
Conclusions:
- METTL3 promotes PLCζ mRNA stability through m6A methylation, ensuring normal sperm expression levels.
- This METTL3-dependent pathway is essential for maintaining fertilization capacity.
- The findings reveal a novel mechanism linking METTL3, m6A modification, PLCζ expression, and male reproductive health, including prostate function.
Related Concept Videos
02:51mRNA Stability and Gene Expression
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
02:51mRNA Stability and Gene Expression
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
01:53RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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...
02:04Covalently Linked Protein Regulators
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.
01:35Pre-mRNA Processing: Modification of pre-mRNA Ends
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps the cell...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps the cell...