METTL16, or Methyltransferase-like protein 16, is a protein found within human cells that performs a specialized chemical modification. This protein acts as an enzyme, facilitating specific reactions within the complex cellular machinery. The instructions for building METTL16 are encoded by the METTL16 gene. Its presence and activity are considered important for the normal functioning of most cells.
The Genetic Blueprint and Its Messengers
Every cell in our body contains a complete set of instructions, known as genes. These genes are made of DNA, a long, double-stranded molecule that stores all the genetic information. DNA resides safely within the cell’s nucleus, serving as the master copy.
To carry out the instructions encoded in DNA, the cell creates temporary working copies in the form of RNA molecules. RNA is similar to DNA but is typically single-stranded and performs a wider variety of functions. Some RNA molecules act as messengers, carrying genetic code from the DNA to cellular machinery that builds proteins. Other types of RNA have direct roles in cellular processes, such as helping to assemble proteins or regulating gene activity. These diverse roles make RNA molecules dynamic players in how a cell operates.
METTL16’s Specific Task: Modifying RNA
METTL16 is categorized as a methyltransferase, a type of enzyme that adds a small chemical tag called a methyl group to other molecules. Its function involves adding N6-methyladenosine (m6A) modifications to specific RNA molecules, influencing how they function.
A key target for METTL16’s m6A modification is U6 small nuclear RNA (U6 snRNA). U6 snRNA is a component of the spliceosome, responsible for splicing. Splicing is a step in gene expression where non-coding regions (introns) are removed from precursor messenger RNA (pre-mRNA), and coding regions (exons) are joined to form mature messenger RNA. METTL16 specifically modifies adenosine at position 43 (m6A43) of U6 snRNA. This modification is important for U6 snRNA’s ability to recognize the 5′ splice site of pre-mRNAs, essential for proper splicing.
The addition of m6A by METTL16 can influence the stability, structure, and interactions of the modified RNA molecule. The modification on U6 snRNA can induce conformational changes. Beyond U6 snRNA, METTL16 also modifies messenger RNA (mRNA) for S-adenosylmethionine (SAM) synthetase (MAT2A), which is involved in regulating cellular SAM levels. METTL16 utilizes S-adenosylmethionine (SAM) as the methyl donor for these modifications.
The Widespread Influence of METTL16
METTL16 activity and its modifications have broad implications for biological processes. Its role in regulating SAM homeostasis, for instance, indirectly affects a wide range of cellular methylation events. This feedback mechanism allows METTL16 to exert control over the overall cellular methylation landscape, even impacting other well-known methyltransferases like METTL3 and METTL14.
Dysregulation of METTL16 has been linked to human health conditions, particularly cancers. For example, in gastric cancer, METTL16 is highly expressed and can promote the proliferation of cancer cells and tumor growth. Its increased expression is associated with a less favorable prognosis in these patients. Mechanistically, METTL16 has been shown to enhance the stability of cyclin D1 mRNA, a protein that promotes cell cycle progression, thereby contributing to tumor growth.
Conversely, in other cancers, such as pancreatic adenocarcinoma, METTL16 may play a tumor-suppressive role. Studies have shown that decreased METTL16 expression is observed in human pancreatic cancer samples, and its overexpression can inhibit the proliferation of pancreatic cancer cells. This suggests a complex role where its impact can vary depending on the specific cancer type. Research is actively ongoing to fully understand the extensive and sometimes seemingly contradictory influence of METTL16 across different cellular contexts and disease states.