Decoding Protein-Methylating METTLs in Humans: Structural, Functional, and Disease Insights over the Past Decade

Area of Science:

• Biochemistry
• Molecular Biology
• Epigenetics

Background:

• Protein methylation is a key post-translational modification regulating cellular functions.
• The methyltransferase-like (METTL) family, structurally similar to arginine methyltransferases, comprises 27 members.
• While some METTLs modify RNA, others target proteins, primarily non-histone lysine residues.

Purpose of the Study:

• To review the current understanding of protein-methylating METTL family members.
• To consolidate knowledge on their structure, targets, localization, and expression.
• To highlight their involvement in diseases like cancer and identify research gaps.

Main Methods:

• Literature review focusing on protein-methylating METTLs.
• Synthesis of data on structural features, enzymatic targets, and sub-cellular localization.
• Analysis of expression patterns and disease relevance, particularly in cancer.

Main Results:

• Protein-methylating METTLs are incompletely characterized despite their discovery over a decade ago.
• Most identified substrates are non-histone proteins, indicating unique functional roles.
• Emerging evidence links METTLs to various diseases, notably cancer.

Conclusions:

• Protein-methylating METTLs play significant roles in cellular regulation and disease.
• Further research is needed to fully elucidate their mechanisms and therapeutic potential.
• Consolidating current knowledge provides a foundation for future investigations into METTL functions.