Abstract
Many proteins with intrinsically disordered regions interact with cytoplasmic ribosomes. However, many of the molecular functions related to these interactions are unclear. In this study, using an abundant RNA-binding protein with a structurally well-defined RNA recognition motif and an intrinsically disordered RGG domain as a model system, we investigated how this protein modulates mRNA storage and translation. Using genomic and molecular approaches, we show that the presence of Sbp1 slows ribosome movement on cellular mRNAs and promotes polysome stalling. Sbp1-associated polysomes display a ring-shaped structure in addition to a beads-on-string morphology visualized under electron microscope. Moreover, post-translational modifications at the RGG motif play important roles in directing cellular mRNAs to either translation or storage. Finally, binding of Sbp1 to the 5'UTRs of mRNAs represses both cap-dependent and cap-independent translation initiation of proteins functionally important for general protein synthesis in the cell. Taken together, our study demonstrates an intrinsically disordered RNA binding protein regulates mRNA translation and storage via distinctive mechanisms under physiological conditions and establishes a framework with which functions of important RGG-proteins can be investigated and defined.