Topic Overview:

The RNA-binding protein La-related protein 1 (LARP1) helps regulate the synthesis of ribosomes, the cellular machines that translate messenger RNAs (mRNAs) into proteins. Ribosomes themselves include many protein subcomponents that are critical for their functioning. The mRNAs that encode these ribosomal proteins, called 5’TOP mRNAs, are chemically distinct from most other mRNA molecules. LARP1 binds 5’TOP mRNAs, thereby controlling to what extent they are available for ribosome biosynthesis.

Elevated LARP1 levels have been implicated in several cancers. To advance their understanding of this potential drug target, Durrant and colleagues have developed and applied computational tools to study LARP1 dynamics and druggability. Their simulation-analysis, molecular-modeling, and visualization methods suggest that the 5’TOP-mRNA binding site is particularly flexible. They have also discovered several other pockets on the LARP1 surface that may bind small-molecule ligands. Better understanding LARP1 dynamics and ligand binding provides pharmacological insights that could lead to novel cancer treatments.