한빛사 논문
Abstract
Seung-Kyoon Kim,1,6 Hosuk Lee,1,6 Kyumin Han,1 Sang Cheol Kim,4 Yoonjung Choi,1 Sang-Wook Park,1 Geunu Bak,3 Younghoon Lee,3 Jung Kyoon Choi,2 Tae-Kyung Kim,5 Yong-Mahn Han,1,* and Daeyoup Lee1,*
1Department of Biological Sciences
2Department of Bio and Brain Engineering
3Department of Chemistry
Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea
4Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Republic of Korea
5Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA
6Co-first author
*Correspondence: Yong-Mahn Han, Daeyoup Lee
Summary
LIN28-mediated processing of the microRNA (miRNA) let-7 has emerged as a multilevel program that controls self-renewal in embryonic stem cells. LIN28A is believed to act primarily in the cytoplasm together with TUT4/7 to prevent final maturation of let-7 by Dicer, whereas LIN28B has been suggested to preferentially act on nuclear processing of let-7. Here, we find that SET7/9 monomethylation in a putative nucleolar localization region of LIN28A increases its nuclear retention and protein stability. In the nucleoli of human embryonic stem cells, methylated LIN28A sequesters pri-let-7 and blocks its processing independently of TUT4/7. The nuclear form of LIN28A regulates transcriptional changes in MYC-pathway targets, thereby maintaining stemness programs and inhibiting expression of early lineage-specific markers. These findings provide insight into the molecular mechanism underlying the posttranslational methylation of nuclear LIN28A and its ability to modulate pluripotency by repressing let-7 miRNA expression in human embryonic stem cells.
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TOP52015년 선정
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