Fig. 4: Model for stepwise maturation of the human mitoribosomal large subunit aided by assembly factors.

Eight classes, corresponding to distinct assembly states in this study, allow us to propose the order of events in the late stages of the human mitoribosomal large subunit assembly. Sequestering of the H68–H71 16S rRNA by assembly factors NSUN4 and MTERF4 exposes the functionally important regions of the large subunit that allows MRM2 to modify its target nucleotide in the A loop. Dissociation of MRM2 is followed by association of MTG2, a mitochondrial GTPase that performs a final quality check of the peptidyl transferase center (PTC) region as well as the sarcin-ricin loop (SRL) in the GTPase-associated center (GAC). Dissociation of all assembly factors, including MALSU1–L0R8F8–mt-ACP (ACP) module, results in the completion of the rRNA maturation and formation of a translationally competent particle.