METTL16, Methyltransferase-Like Protein 16: Current Insights into Structure and Function

Area of Science:

• Molecular Biology
• RNA Biology
• Biochemistry

Background:

• Methyltransferase-like protein 16 (METTL16) is a human RNA methyltransferase.
• It installs m⁶A marks on U6 small nuclear RNA (U6 snRNA) and S-adenosylmethionine (SAM) synthetase pre-mRNA.
• METTL16 regulates SAM homeostasis, impacting the m⁶A epitranscriptome.

Purpose of the Study:

• To summarize current knowledge on METTL16 within the context of human m⁶A RNA methyltransferases.
• To highlight structural and functional insights into METTL16 activity and substrate interactions.
• To contextualize METTL16's role alongside other recently identified m⁶A methyltransferases.

Main Methods:

• Review of existing structural and functional studies of METTL16.
• Analysis of molecular structures of METTL16 domains (apo, SAH, RNA complexes).
• Investigation of vertebrate-conserved regions (VCRs) in U6 snRNA interaction.

Main Results:

• Structural data elucidate METTL16's interaction with coenzymes and substrates, revealing autoinhibitory mechanisms.
• VCRs are crucial for U6 snRNA binding.
• METTL16 interacts with diverse RNA classes (mRNA, ncRNA, lncRNA, rRNA), including oncogenic MALAT1, suggesting RNA triple helix recognition.
• The number of known human m⁶A methyltransferases has expanded significantly.

Conclusions:

• METTL16 is a significant player in the human m⁶A RNA methyltransferase landscape.
• Structural and functional studies provide a basis for understanding METTL16's regulatory roles.
• METTL16's diverse RNA interactions underscore its broad impact on epitranscriptomics.