RNAmetasome network for macromolecule biogenesis in human cells

• Published in: Communications biology Vol. 4; no. 1; p. 1399
• Main Authors: Iuchi, Shiro, Paulo, Joao A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.12.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/109; 13/89; 14; 14/19; 14/34; 631/337/1645; 631/80/83; 82; 82/29; 82/58; ATPases Associated with Diverse Cellular Activities - genetics; ATPases Associated with Diverse Cellular Activities - metabolism; Biology; Biomedical and Life Sciences; Biosynthesis; Cell cycle; Cell proliferation; Cell Proliferation - genetics; Chromatin remodeling; Gene expression; Gene Expression - physiology; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; HEK293 Cells; Humans; Immunocytochemistry; Immunoprecipitation; Ki-67 Antigen - genetics; Ki-67 Antigen - metabolism; Life Sciences; Metabolic networks; Metabolic Networks and Pathways; Metabolism; Proteins; RNA - metabolism; RNA processing
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02928-y

RNA plays a central role in macromolecule biogenesis for various pathways, such as gene expression, ribosome biogenesis, and chromatin remodeling. However, RNA must be converted from its nascent to functional forms for that role. Here, we describe a large RNA metabolic network (RNAmetasome network) for macromolecule biogenesis in human cells. In HEK293T, the network consists of proteins responsible for gene expression, splicing, ribosome biogenesis, chromatin remodeling, and cell cycle. Reciprocal immunoprecipitations show that MKI67, GNL2, MDN1, and ELMSAN1 are core proteins of the network, and knockdown of either MKI67 or GNL2 affects the state of the other protein, MDN1, and some other network members. Furthermore, GNL2 knockdown retards cell proliferation. Several proteins of the RNAmetasome network are diminished in Hela.cl1, and this diminishment is associated with low expression of MDN1 and elevated MKI67 degradation. These results together suggest that the RNAmetasome network is present in human cells and associated with proliferation, and that MKI67, GNL2, and MDN1 play an important role in organizing the RNAmetasome network. Iuchi and Paulo identify a large metabolic complex for macromolecule biogenesis composed of numerous RNA processing proteins in HEK293T cells, which the authors term the RNAmetasome. The authors identify the complex by mass-spec using ELMSAN1 as bait and utilize reciprocal immunoprecipitation and immunocytochemistry for validation, and find that MKI67, GNL2, and MDN1 have important roles organizing the RNAmetasome network.