On July 31st 2021, Zhen Sun et.al. from Dr. Jin Zhang’s group published LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells at Protein&Cell.

LIN28 is an RNA binding protein with important rolesin early embryo development, stem cell differentiation/reprogramming,tumorigenesis and metabolism. Previous studies have focused mainly on its rolein the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, andfew have addressed LIN28's role within the nucleus. Here, we show that LIN28displays dynamic temporal and spatial expression during murine embryodevelopment. Maternal LIN28 expression drops upon exit from the 2-cell stage,and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell toblastocyst stage development, to become dominantly expressed in the cytosolafter implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptionalprogram characterized by the expression of endogenous retrovirus genes.Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintainnucleolar integrity, and its loss leads to nucleolar phase separation defects,ribosomal stress and activation of P53 which in turn binds to and activates 2Ctranscription factor Dux. LIN28 also resides in a complex containing thenucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, andLIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux andrDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28knockout cells with nucleolar stress are more likely to assume a slowlycycling, translationally inert and anabolically inactive state, which is a partof previously unappreciated 2C-like transcriptional program. These findingselucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking2C program and nucleolar functions in PSCs and early embryo development.