Engineered Ribonucleoprotein Granules Inhibit Translation in Protocells

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Liquid granules composed of intrinsically disordered proteins (IDPs) and RNA are crucial for cellular functions like RNA processing and translation.
• The precise mechanisms governing these processes within granules are not fully understood.
• Developing artificial granules could offer external control over cellular translation.

Purpose of the Study:

• To engineer de novo artificial ribonucleoprotein granules for controlled translation.
• To investigate the role of intrinsically disordered proteins in granule formation and function.
• To elucidate the mechanisms of translation inhibition by artificial granules.

Main Methods:

• Engineered a recombinant RNA-binding intrinsically disordered protein with tunable phase behavior in water.
• Developed a kinetic model to simulate granule-mediated translation inhibition.
• Experimentally demonstrated temporal translation inhibition within monodisperse droplets using designer IDPs.

Main Results:

• Successfully created artificial ribonucleoprotein granules from a designer IDP.
• The kinetic model indicated translation inhibition via mRNA sequestration (reversible or irreversible).
• Experimental results confirmed temporal inhibition of translation by tunable IDPs within droplets.

Conclusions:

• This work establishes a bottom-up approach for engineering artificial ribonucleoprotein granules.
• The findings provide a foundation for understanding and controlling translation through synthetic granules.
• The developed artificial granules offer a promising tool for mechanistic studies of natural granules.