Understanding GEMIN5 Interactions: From Structural and Functional Insights to Selective Translation.

Abstract

GEMIN5 is a predominantly cytoplasmic protein, initially identified as a member of the survival of motor neurons (SMN) complex. In addition, this abundant protein modulates diverse aspects of RNA-dependent processes, executing its functions through the formation of multi-component complexes. The modular organization of structural domains present in GEMIN5 enables this protein to perform various functions through its interaction with distinct partners. The protein is responsible for the recognition of small nuclear (sn)RNAs through its N-terminal region, and therefore for snRNP assembly. Beyond its role in spliceosome assembly, GEMIN5 regulates translation through the interaction with either RNAs or proteins. In the central region, a robust dimerization domain acts as a hub for protein-protein interaction, while a non-canonical RNA-binding site is located towards the C-terminus. Interestingly, GEMIN5 regulates the partitioning of mRNAs into polysomes, likely due to its RNA-binding capacity and its ability to bind native ribosomes. Understanding the functional and structural organization of the protein has brought an increasing interest in the last years with important implications in human disease. Patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. This review discusses recent relevant works aimed at understanding the molecular mechanisms of GEMIN5 activity in gene expression, and also the challenges to discover new functions.