Ribosomal proteins L5 and L11 co-operatively inactivate c-Myc via RNA-induced silencing complex

Area of Science:

• Molecular Biology
• Cancer Biology
• Gene Regulation

Background:

• The oncogene MYC is frequently overexpressed in human cancers.
• MYC regulates ribosome biogenesis, a process critical for cell growth.
• Ribosomal protein L11 (RPL11) was previously shown to inhibit MYC activity under ribosomal stress.

Purpose of the Study:

• To investigate the role of ribosomal protein L5 (RPL5) in regulating MYC expression.
• To elucidate the mechanism by which RPL5 and RPL11 control MYC activity.
• To understand the implications for ribosome biogenesis and cancer.

Main Methods:

• Knockdown and overexpression of RPL5 in cells.
• Immunoprecipitation assays to detect protein-RNA interactions.
• Analysis of MYC mRNA and protein levels.
• Assessment of RNA-induced silencing complex (RISC) components.

Main Results:

• RPL5, together with RPL11, directs RISC to MYC mRNA, promoting its degradation.
• RPL5 binds to the 3'UTR of MYC mRNA and RISC subunits (TRBP, Ago2).
• Loss of RPL5 increases MYC expression, while RPL5 overexpression suppresses it.

Conclusions:

• RPL5 and RPL11 cooperatively suppress MYC expression through mRNA degradation mediated by RISC.
• This mechanism provides a novel pathway for controlling MYC levels and ribosome biogenesis.
• Targeting this pathway could offer therapeutic strategies for MYC-driven cancers.