Global translation during early development depends on the essential transcription factor PRDM10

• Published in: Nature communications Vol. 11; no. 1; p. 3603
• Main Authors: Han, Brenda Y., Seah, Michelle K. Y., Brooks, Imogen R., Quek, Delia H. P., Huxley, Dominic R., Foo, Chuan-Sheng, Lee, Li Ting, Wollmann, Heike, Guo, Huili, Messerschmidt, Daniel M., Guccione, Ernesto
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-07-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 13/2; 38/39; 45/15; 45/91; 631/136; 631/337; Animals; Embryo cells; Embryogenesis; Embryonic Development; Embryonic growth stage; Embryonic Stem Cells - metabolism; Embryos; Eukaryotic Initiation Factors - genetics; Eukaryotic Initiation Factors - metabolism; Female; Gene Expression Regulation, Developmental; Homeostasis; Humanities and Social Sciences; Implantation; Initiation factor eIF-3; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Male; Mice - embryology; Mice - genetics; Mice - metabolism; multidisciplinary; Protein Biosynthesis; Regulators; Science; Science (multidisciplinary); Stem cells; Surgical implants; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Translation; Zinc finger proteins
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-17304-3

Members of the PR/SET domain-containing (PRDM) family of zinc finger transcriptional regulators play diverse developmental roles. PRDM10 is a yet uncharacterized family member, and its function in vivo is unknown. Here, we report an essential requirement for PRDM10 in pre-implantation embryos and embryonic stem cells (mESCs), where loss of PRDM10 results in severe cell growth inhibition. Detailed genomic and biochemical analyses reveal that PRDM10 functions as a sequence-specific transcription factor. We identify
Eif3b
, which encodes a core component of the eukaryotic translation initiation factor 3 (eIF3) complex, as a key downstream target, and demonstrate that growth inhibition in PRDM10-deficient mESCs is in part mediated through EIF3B-dependent effects on global translation. Our work elucidates the molecular function of PRDM10 in maintaining global translation, establishes its essential role in early embryonic development and mESC homeostasis, and offers insights into the functional repertoire of PRDMs as well as the transcriptional mechanisms regulating translation.
PRDM family members are transcriptional regulators involved in cell identity and fate determination. Here, the authors characterize PRDM10 and show that it functions to ensure global translation efficiency during early embryonic development.