Impact of RNA–Protein Interaction Modes on Translation Control: The Versatile Multidomain Protein Gemin5

The fate of cellular RNAs is largely dependent on their structural conformation, which determines the assembly of ribonucleoprotein (RNP) complexes. Consequently, RNA‐binding proteins (RBPs) play a pivotal role in the lifespan of RNAs. The advent of highly sensitive in cellulo approaches for studying RNPs reveals the presence of unprecedented RNA‐binding domains (RBDs). Likewise, the diversity of the RNA targets associated with a given RBP increases the code of RNA–protein interactions. Increasing evidence highlights the biological relevance of RNA conformation for recognition by specific RBPs and how this mutual interaction affects translation control. In particular, noncanonical RBDs present in proteins such as Gemin5, Roquin‐1, Staufen, and eIF3 eventually determine translation of selective targets. Collectively, recent studies on RBPs interacting with RNA in a structure‐dependent manner unveil new pathways for gene expression regulation, reinforcing the pivotal role of RNP complexes in genome decoding. Gemin5 is a cytoplasmic protein with noncanonical RNA‐binding domains (RBDs). An RBD located on the WD40 motifs negatively regulates translation, besides interacting with the ribosome. The RBS1 domain recognizes targets with a stable secondary structure, stimulating translation and counteracting the negative effect of Gemin5 on translation. Finally, the RBS2 domain selectively downregulates internal ribosome entry site (IRES)‐driven translation.