Roles of MKI67, GNL2, and MDN1 in Chromosome Organization, Nucleolar Function, and Transcriptome Regulation

The MGM complex, comprising the MKI67 (Ki-67), GNL2, and MDN1 proteins, plays a crucial role in RNA metabolism. However, the functions of these proteins are largely unknown. Here, we describe their functions. MKI67 binds to proliferating-cell chromosomes through consensus sequences and primarily localizes at the nucleolar periphery. Peripheral MKI67 maintains pre- 60S particles in the nucleolus and then releases them into the nucleus by recruiting MDN1 via GNL2. This MKI67 also appears to be essential for importing nucleolar proteins and protein complexes. Furthermore, it is associated with organizing acrocentric and non-acrocentric chromosomes. Additionally, MKI67 regulates the levels of numerous genomic transcripts, including UNC13A and NEK7. MKI67 downregulates UNC13A during transcription and downregulates NEK7 by involving mRNA degradation systems. MKI67 knockdown upregulates SLC7A2 transcripts and its paralogs. These transcripts are known to activate mTORC1 and increase protein synthesis and proliferation. This finding implies that the absence of MKI67 enables differentiated tissue cells to live longer and perform their cell-type-specific activities. MDN1 knockdown downregulates the pre-60S particle-related RNAs and respiratory complex transcripts. This indicates the existence of a mechanism that prevents wasteful energy production when ribosome biosynthesis decreases. Collectively, MKI67, GNL2, and MDN1 regulate chromosome organization, nucleolar function, and transcriptomes.