[7SK truncation at 128-179 nt suppresses embryonic stem cell proliferation in vitro by downregulating CDC6]

Rui Chen1, Yurong Zhang1, Peng Chen2

  • 1First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, China.

Abstract

Insights

Small nuclear RNA 7SK truncation impairs embryonic stem cell (ESC) proliferation by downregulating CDC6. This finding highlights 7SK

Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • Embryonic stem cells (ESCs) possess self-renewal and differentiation capabilities.
  • Primordial dwarfism (PD) is a group of rare genetic disorders characterized by severe intrauterine and postnatal growth retardation.
  • Small nuclear noncoding RNA 7SK plays a role in various cellular processes.

Purpose of the Study:

  • To investigate the function of small nuclear noncoding RNA 7SK in ESC proliferation.
  • To evaluate the potential of 7SK as a diagnostic and therapeutic target for primordial dwarfism (PD).

Main Methods:

  • CRISPR/Cas9 gene editing was used to create 7SK deletion mutations in R1 ESCs.
  • Lentivirus-mediated knockdown of cyclin-dependent kinase 9 (CDK9) was performed.
  • Western blotting was employed to analyze protein expression levels, including CDC6.

Main Results:

  • A novel 7SK deletion mutation (128-179 nt) was identified in ESCs, leading to deficient cell proliferation.
  • 7SK truncation significantly reduced the expression of La-related protein 7 (LARP7) and cell division cycle 6 (CDC6).

Conclusions:

  • 7SK truncation at 128-179 nt impairs ESC proliferation by downregulating CDC6.
  • 7SK is a critical regulator of ESC proliferation, mediated by CDK9 activity.
  • 7SK truncation presents a potential target for the early diagnosis and treatment of primordial dwarfism.

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