Three's a crowd - why did three N-terminal methyltransferases evolve for one job?

Area of Science:

• Biochemistry
• Molecular Biology
• Post-Translational Modifications

Background:

• N-terminal methylation (Nα-methylation) is a post-translational modification (PTM) with over 300 predicted substrates.
• Three mammalian Nα-methyltransferases exist: METTL11A, METTL11B (NTMT1, NTMT2), and METTL13.
• METTL11A methylates most substrates, while METTL13 has one known substrate, and METTL11B has no proven unique targets.

Purpose of the Study:

• To investigate the distinct expression, localization, and physiological roles of the three Nα-methyltransferases.
• To compare these characteristics with other methyltransferases, including those with non-catalytic functions.
• To hypothesize the unique cellular functions of each Nα-methyltransferase.

Main Methods:

• Comparative analysis of Nα-methyltransferase expression patterns.
• Examination of subcellular localization of METTL11A, METTL11B, and METTL13.
• Literature review and comparison with methyltransferases possessing non-catalytic functions.

Main Results:

• Significant differences in expression and localization were observed among the three Nα-methyltransferases.
• Each enzyme exhibits unique physiological roles, distinct from simple catalytic activity.
• Comparisons suggest non-catalytic functions are crucial for methyltransferases.

Conclusions:

• The three Nα-methyltransferases likely evolved for distinct, specialized cellular functions, not redundant catalytic roles.
• Understanding these unique jobs is key to deciphering the global roles of these proteins.
• Nα-methyltransferases may represent an emerging class of enzymes with significant non-catalytic functions.