Many Faces of TRIM Proteins on the Road from Pluripotency to Neurogenesis.

Tripartite motif (TRIM) proteins participate in numerous biological processes. They are the key players in immune system and are involved in the oncogenesis. Moreover, TRIMs are the highly conserved regulators of developmental pathways in both vertebrates and invertebrates. In particular, numerous data point to the participation of TRIMs in the determination of stem cell fate, as well as in the neurogenesis. TRIMs apply various mechanisms to perform their functions. Their common feature is the ability to ubiquitinate proteins mediated by the Really Interesting New Gene (RING) domain. Different C-terminal domains of TRIMs are involved in DNA and RNA binding, protein/protein interactions, and chromatin-mediated transcriptional regulation. Mutations and alterations of TRIM expression cause significant disturbances in the stem cells' self-renewal and neurogenesis, which result in the various pathologies of the nervous system (neurodegeneration, neuroinflammation, and malignant transformation). This review discusses the diverse molecular mechanisms of participation of TRIMs in stem cell maintenance and self-renewal as well as in neural differentiation processes and neuropathology.