METTL16 promotes translation and lung tumorigenesis by sequestering cytoplasmic eIF4E2

Area of Science:

• Molecular Biology
• RNA Biology
• Cancer Research

Background:

• N6-methyladenosine (m6A) is a key epigenetic RNA modification regulating RNA metabolism.
• METTL16 is known as a nuclear m6A methyltransferase, but its cytoplasmic role is unclear.

Purpose of the Study:

• To investigate the role of METTL16 in cytoplasmic RNA fate and protein synthesis.
• To elucidate the mechanism by which METTL16 influences translation.
• To explore METTL16 as a potential therapeutic target in lung cancer.

Main Methods:

• Detection of METTL16 subcellular localization (nucleus and cytoplasm).
• Assessment of protein synthesis upon METTL16 depletion.
• Identification of METTL16 interacting partners using biochemical assays.
• Analysis of METTL16's effect on oncogene translation in lung cancer models.

Main Results:

• METTL16 exhibits dual localization in both the nucleus and cytoplasm.
• METTL16 depletion reduces protein synthesis, independent of its methyltransferase activity.
• METTL16 interacts with eIF4E2, inhibiting its translation repression activity.
• METTL16 promotes cap recognition by eIF4E, enhancing selective protein synthesis.
• METTL16 depletion suppresses lung tumorigenesis by downregulating oncogene translation.

Conclusions:

• METTL16 plays a significant role in regulating cytoplasmic translation.
• The interaction between METTL16 and eIF4E2 is crucial for promoting protein synthesis.
• METTL16 represents a promising therapeutic target for lung cancer treatment.