PMID- 32323360
OWN - NLM
STAT- MEDLINE
DCOM- 20210115
LR  - 20211204
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 34
IP  - 6
DP  - 2020 Jun
TI  - Transient inhibition of rDNA transcription in donor cells improves ribosome 
      biogenesis and preimplantation development of embryos derived from somatic cell 
      nuclear transfer.
PG  - 8283-8295
LID - 10.1096/fj.202000025RR [doi]
AB  - Ribosomal DNA (rDNA) transcription is a limiting step in ribosome biogenesis, 
      crucial for protein synthesis and cell growth-especially at the early stages of 
      embryonic development-and is regulated in a mammalian target of rapamycin 
      (mTOR)-dependent manner. Our previous report demonstrated that treatment with 
      mTOR inhibitors during artificial embryonic activation improved the development 
      of embryos derived from somatic cell nuclear transfer (SCNT). We hypothesize that 
      inhibition of ribosome biogenesis in somatic cells facilitates reactivation of 
      embryonic nucleolar establishment and ribosome biogenesis in SCNT embryos. 
      Herein, we show that mTOR inhibitors suppressed ribosome biogenesis in somatic 
      cells, and more importantly, improved development potential of SCNT embryos 
      (blastocyst rate, 34% vs 24%). SCNT embryos derived from drug-treated somatic 
      cells exhibited higher levels of 47S, 18S, and 5S rRNAs, upstream binding factor 
      (UBF) mRNA, ribosomal protein S6; they also improved the rebuilding of the 
      nucleolar ultrastructure. In addition, treatment of donor cells with the RNA 
      polymerase I (Pol I) inhibitor cx5461 caused similar effects on SCNT embryos. 
      These results indicated that transient inhibition of rDNA transcription in donor 
      cells facilitated the establishment of functional nucleoli and improved 
      preimplantation development of SCNT embryos.
CI  - (c) 2020 Federation of American Societies for Experimental Biology.
FAU - Liao, Chen
AU  - Liao C
AD  - Department of Histology and Embryology, Harbin Medical University, Harbin, China.
FAU - Pang, Nan
AU  - Pang N
AD  - Department of Histology and Embryology, Harbin Medical University, Harbin, China.
FAU - Liu, Zhaojun
AU  - Liu Z
AD  - Department of Histology and Embryology, Harbin Medical University, Harbin, China.
FAU - Lei, Lei
AU  - Lei L
AD  - Department of Histology and Embryology, Harbin Medical University, Harbin, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200422
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (DNA, Ribosomal)
RN  - 0 (Pol1 Transcription Initiation Complex Proteins)
RN  - 0 (transcription factor UBF)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Blastocyst/physiology
MH  - Cell Nucleolus/*genetics
MH  - Cloning, Organism/methods
MH  - DNA, Ribosomal/*genetics
MH  - Embryo, Mammalian/physiology
MH  - Embryonic Development/*genetics
MH  - Female
MH  - Mice
MH  - Nuclear Transfer Techniques
MH  - Organelle Biogenesis
MH  - Pol1 Transcription Initiation Complex Proteins/genetics
MH  - Ribosomes/*genetics
MH  - TOR Serine-Threonine Kinases/genetics
MH  - Transcription, Genetic/*genetics
OTO - NOTNLM
OT  - SCNT
OT  - cx5461
OT  - mTOR inhibitor
OT  - nucleolar rebuilding
OT  - rDNA transcription
EDAT- 2020/04/24 06:00
MHDA- 2021/01/16 06:00
CRDT- 2020/04/24 06:00
PHST- 2020/01/06 00:00 [received]
PHST- 2020/04/07 00:00 [revised]
PHST- 2020/04/09 00:00 [accepted]
PHST- 2020/04/24 06:00 [pubmed]
PHST- 2021/01/16 06:00 [medline]
PHST- 2020/04/24 06:00 [entrez]
AID - 10.1096/fj.202000025RR [doi]
PST - ppublish
SO  - FASEB J. 2020 Jun;34(6):8283-8295. doi: 10.1096/fj.202000025RR. Epub 2020 Apr 22.