7SK truncation at 128-179 nt suppresses embryonic stem cell proliferation
10.12122/j.issn.1673-4254.2021.08.01
- Author:
Rui CHEN
1
;
Yurong ZHANG
1
;
Peng CHEN
2
;
Yixin PANG
3
;
Hongbao LI
4
;
Ziwei CHEN
5
;
Xiaoyong ZHANG
1
;
Hongyi ZHANG
1
;
Wujun LI
1
Author Information
1. First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, China.
2. Institute of Basic Medical Science, Xi'an Medical University, Xi'an 710021, China.
3. Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
4. Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an 710061, China.
5. School of Clinical Medicine, Xi'an MedicalUniversity, Xi'an710021, China.
- Publication Type:Journal Article
- Keywords:
7SK truncation;
cell division cycle 6;
cyclin-dependent kinase 9;
embryonic stem cell;
proliferation
- MeSH:
Cell Cycle Proteins;
Cell Proliferation;
Embryonic Stem Cells/metabolism*;
HeLa Cells;
Humans;
Nuclear Proteins;
Positive Transcriptional Elongation Factor B/metabolism*;
RNA, Long Noncoding/genetics*;
RNA-Binding Proteins;
Ribonucleoproteins;
Transcription Factors
- From:
Journal of Southern Medical University
2021;41(8):1125-1130
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the role of small nuclear noncoding RNA 7SK in embryonic stem cell (ESCs) proliferation and the value of 7SK as a target for early diagnosis and treatment for primordial dwarfism (PD).
METHODS:ESC line R1 was transfected with the CRISPR/Cas9 system, and sequencing of the PCR product and glycerol gradient analysis were performed to identify novel 7SK deletion mutations. A lentivirus system was used to knock down cyclin-dependent kinase 9 (CDK9) in clones with 7SK deletion mutations, and the effect of CDK9 knockdown on the protein level of cell division cycle 6 (CDC6) was analyzed with Western blotting.
RESULTS:We identified a novel deletion mutation of 7SK at 128-179 nt in the ESCs, which resulted in deficiency of cell proliferation. 7SK truncation at 128-179 nt significantly reduced the protein expressions of La-related protein 7 (LARP7) and CDC6.
CONCLUSIONS:7SK truncation at 128-179 nt can significantly impair proliferation of ESCs by downregulating CDC6. 7SK is a key regulator of proliferation and mediates the growth of ESCs through a mechanism dependent on CDK9 activity, suggesting the value of 7SK truncation at 128-179 nt as a potential target for early diagnosis and treatment of PD.
