Widespread changes in protein synthesis induced by microRNAs

Area of Science:

• Molecular Biology
• Genetics
• Proteomics

Background:

• Animal microRNAs (miRNAs) are known regulators of gene expression, primarily through mRNA degradation or translation inhibition.
• The genome-wide extent of translational control exerted by miRNAs remains largely uncharacterized.

Purpose of the Study:

• To quantitatively assess the impact of miRNAs on protein synthesis at a genome-wide scale using a novel proteomic approach.
• To investigate the relationship between miRNA activity, mRNA levels, and protein production.

Main Methods:

• Utilized a proteomic technique to measure protein synthesis changes following miRNA transfection or knockdown.
• Employed microarrays to simultaneously quantify mRNA levels.
• Analyzed miRNA-binding site characteristics influencing protein synthesis repression.

Main Results:

• A single miRNA can repress the production of hundreds of proteins, though typically with mild effects.
• Identified specific target sequence features, beyond the seed sequence, that influence miRNA-mediated repression of human protein synthesis.
• Demonstrated that miRNAs directly repress translation of hundreds of genes, in addition to affecting mRNA levels.

Conclusions:

• miRNAs exert significant translational control over protein synthesis on a genome-wide scale.
• miRNAs can modulate protein output from thousands of genes through direct and indirect mechanisms.