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LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells by Zhen Sun; Hua Yu; Jing Zhao; Tianyu Tan; Hongru Pan; Yuqing Zhu; Lang Chen; Cheng Zhang; Li Zhang; Anhua Lei; Yuyan Xu; Xianju Bi; Xin Huang; Bo Gao; Longfei Wang; Cristina Correia; Ming Chen; Qiming Sun; Yu Feng; Li Shen; Hao Wu; Jianlong Wang; Xiaohua Shen; George Q. Daley; Hu Li; Jin Zhang is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with __Let-7__ microRNA precursors or mRNAs, and few have addressed LIN28’s role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor __Dux__. LIN28 also resides in a complex containing th

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Author

Zhen Sun; Hua Yu; Jing Zhao; Tianyu Tan; Hongru Pan; Yuqing Zhu; Lang Chen; Cheng Zhang; Li Zhang; Anhua Lei; Yuyan Xu; Xianju Bi; Xin Huang; Bo Gao; Longfei Wang; Cristina Correia; Ming Chen; Qiming Sun; Yu Feng; Li Shen; Hao Wu; Jianlong Wang; Xiaohua Shen; George Q. Daley; Hu Li; Jin Zhang

Publisher

Oxford University Press (OUP)

Published

2021

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)