Mechanistic study of regulation of let-7 miRNA biogenesis by LIN28A in the nucleus = 핵 내에서의 LIN28A에 의한 let-7 마이크로 RNA 조절에 관한 연구

LIN28A has emerged as a key regulator of various biological pathways in embryonic stem cells (ESCs), however the regulatory mechanism by which LIN28A-mediated miRNA processing in the nucleus contributes to pluripotency is largely unknown. Here, we show that SET7/9, a histone mono-methyltransferase, associates with LIN28A. SET7/9-mediated methylation increases LIN28A nuclear reten-tion and protein stability as well as multimerization of nuclear LIN28A to pri-let-7 miRNA. Using an RNAi knockdown approach, we reveal that nuclear LIN28A functions in the nucleoli of ESCs by sequestering the pri-let-7 and blocking its processing via a TUTase-independent mechanism. The nuclear LIN28A regulates transcriptional changes of MYC-pathway targets through maximum inhibition of let-7 biogenesis, thereby maintaining stemness and inhibiting differentiation by modulating stem cell and early lineage-specific mark-ers. These findings provide new insight into the molecular mechanism underlying the post-translational meth-ylation of nuclear LIN28A and its ability to modulate pluripotency by controlling pri-let-7 miRNAs in human ESCs.
Advisors
Lee, Daeyoupresearcher이대엽researcher
Publisher
한국과학기술원
Issue Date
2016
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2016.2 ,[vi, 116 p. :]

Keywords

LIN28A; LIN28B; SET7/9; let-7 miRNA; TUTase; let-7 마이크로 RNA

URI
http://hdl.handle.net/10203/222114
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=648153&flag=t
Appears in Collection
BS-Theses_Ph.D.(박사논문)
Files in This Item
There are no files associated with this item.
  • Hit : 80
  • Download : 0
  • Cited 0 times in thomson ci

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0