@article{05b8c0650f104ab1932d6b3a78af6f41,
title = "SET7/9 methylation of the pluripotency factor LIN28A is a nucleolar localization mechanism that blocks let-7 biogenesis in human ESCs",
abstract = "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.",
author = "Kim, {Seung Kyoon} and Hosuk Lee and Kyumin Han and Kim, {Sang Cheol} and Yoonjung Choi and Park, {Sang Wook} and Geunu Bak and Younghoon Lee and Choi, {Jung Kyoon} and Kim, {Tae Kyung} and Han, {Yong Mahn} and Daeyoup Lee",
note = "Funding Information: We thank Drs. Ryan D. Mohan and Tamaki Suganuma for critical readings and discussions. We wish to acknowledge V. Narry Kim for kindly providing the pRL-CMV, pGL3-CMV-let-7a binding sites, pGL3-CMV-miR-16 binding site, and pCK-FLAG-AGO2 constructs. This work was supported by grants from the Stem Cell Research Program (2011-0019509 and 2012M 3A9B 4027953), the Basic Science Research Program (NRF-2012R1A6A3A01038981), the KAIST Future Systems Healthcare Project, and the Intelligent Synthetic Biology Center of Global Frontier Project funded by the Ministry of Science, ICT and Future Planning (2011-0031955). This work was also funded by the Welch Foundation (I-1786), the Klingenstein Fund, and grant R01NS085418 from the National Institute of Neurological Disorders and Stroke (T.-K.K.). Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",
year = "2014",
month = dec,
day = "4",
doi = "10.1016/j.stem.2014.10.016",
language = "English (US)",
volume = "15",
pages = "735--749",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "6",
}