Structure, Dynamics and Assembly of Human Antimicrobial Protein
More than 2,700 human mRNA 3′UTRs have hundreds of highly conserved (HC) nucleotides, but their biological roles are unclear. A large fraction of mRNAs with highly conserved 3′UTRs
encodes proteins with long intrinsically disordered regions (IDRs). For the tested candidates, we observed that these proteins are only fully active when translated from mRNA templates that include their 3′UTRs, raising the possibility of functional interactions between 3′UTRs and IDRs. Rather than affecting protein abundance or localization, we find that highly conserved 3′UTRs directly control protein activity through protein folding of IDR-containing proteins. Presence of the 3′UTR is required to prevent interference of hydrophobic clusters in the IDR with the folding of the structured domains of the mRNA-encoded protein. In addition to folding of individual proteins, we also observed that for some transcription factors 3′UTR-3′UTR interactions determine the co-folding of the mRNA-encoded proteins, thus generating stable heterodimers. Taken together, our work indicates that highly conserved 3′UTRs regulate protein activity in an abundance-independent manner, by controlling different co-translational protein folding pathways.
Please use this link to access Zoom.