Lin28, a major translation reprogramming factor, gains access to YB-1-packaged mRNA through its cold-shock domain

Area of Science:

• Molecular Biology
• Cell Biology
• Cancer Research

Background:

• Lin28 (Lin28a) is an RNA-binding protein crucial for pluripotency, regulating translation and promoting cancer.
• While Lin28 inhibits let-7 microRNA maturation, its direct binding to numerous cytoplasmic mRNAs suggests broader regulatory roles.
• The mechanism by which Lin28 reprograms global translation through mRNA processing remains largely unknown.

Purpose of the Study:

• To elucidate the mechanism by which Lin28 regulates mRNA processing and reprograms global translation.
• To investigate the potential interaction between Lin28 and other RNA-binding proteins involved in translation regulation.

Main Methods:

• Structural and cellular approaches were employed to study protein interactions.
• The study focused on the interaction between Lin28 and YB-1 (YBX1) in the presence of mRNA.
• Comparative analysis was performed with other RNA-binding proteins lacking cold-shock domains (HuR, G3BP-1, FUS, LARP-6).

Main Results:

• Lin28 was observed to mix with YB-1 in the presence of mRNA, mediated by their respective cold-shock domains.
• This interaction was specific, as other tested RNA-binding proteins without cold-shock domains did not mix with YB-1.
• YB-1 is identified as a core component of dormant messenger ribonucleoprotein complexes (mRNPs).

Conclusions:

• A model is proposed where Lin28 accesses mRNPs via co-association with YB-1, enabling the reprogramming of translation.
• This interaction with mRNPs may explain Lin28's role in development and cancer cell adaptation to stress.
• The findings highlight the importance of mRNP plasticity in Lin28-mediated cellular functions.