SET7/9 methylation of the pluripotency factor LIN28A is a nucleolar localization mechanism that blocks let-7 biogenesis in human ESCs.
SCIE
SCOPUS
- Title
- SET7/9 methylation of the pluripotency factor LIN28A is a nucleolar localization mechanism that blocks let-7 biogenesis in human ESCs.
- Authors
- KIM, TAE KYUNG
- Date Issued
- 2014-12-04
- Publisher
- CELL PRESS
- 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 post-translational methylation of nuclear LIN28A and its ability to modulate pluripotency by repressing let-7 miRNA expression in human embryonic stem cells.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/94315
- DOI
- 10.1016/j.stem.2014.10.016
- ISSN
- 1934-5909
- Article Type
- Article
- Citation
- Cell Stem Cell, vol. 15, no. 6, page. 735 - 749, 2014-12-04
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