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Mmu-miR-702 functions as an anti-apoptotic mirtron by mediating ATF6 inhibition in mice

Wei-Guang Zhang1, Lin Chen, Qin Dong

  • 1Department of Biochemistry and Molecular Biology, Basic Medical Science College, Harbin Medical University, Harbin 150081, China.

Gene
|September 17, 2013
PubMed

Insights

Mouse miR-702 (mmu-miR-702), a small noncoding RNA, inhibits apoptosis by regulating activating transcription factor 6 (ATF6). This study reveals mirtrons

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • MicroRNAs (miRNAs) are crucial post-transcriptional regulators involved in diverse biological processes, including apoptosis.
  • Mirtrons, a class of small noncoding RNAs, are derived from introns and their roles in cellular regulation are emerging.
  • Apoptosis, or programmed cell death, is a fundamental process tightly controlled by gene expression.

Purpose of the Study:

  • To investigate the role of mouse miR-702 (mmu-miR-702) in regulating apoptosis.
  • To identify the molecular targets of mmu-miR-702 involved in apoptotic pathways.
  • To explore the potential function of mirtrons in apoptosis regulation.

Main Methods:

  • Quantitative real-time PCR to assess mmu-miR-702 expression.
  • Over-expression studies to evaluate the effect of mmu-miR-702 on apoptosis.
  • Luciferase reporter assays to confirm gene interactions.
  • Western blot analysis to detect protein expression levels.

Main Results:

  • mmu-miR-702 expression was significantly down-regulated by the apoptosis-inducer isoproterenol in vivo and in vitro.
  • Over-expression of mmu-miR-702 inhibited apoptosis and reduced the expression of apoptosis-related genes.
  • Activating transcription factor 6 (ATF6) was identified as a direct target of mmu-miR-702, confirmed by luciferase and western blot assays.
  • This study reports the first direct interaction between ATF6 and any miRNA.

Conclusions:

  • mmu-miR-702 acts as a negative regulator of apoptosis, potentially through targeting ATF6.
  • Mirtrons, including mmu-miR-702, play a role in the intricate process of apoptosis.
  • These findings suggest mirtrons as a novel area for apoptosis research and therapeutic strategies.
Keywords:
78kDa glucose-regulated proteinATF6ApoptosisB-cell CLL/lymphoma 2BAXBCL2BCL2-associated X proteinC/EBP homologous proteinCHOPERERSEGRP78ISOIsoproterenolMicroRNAShort hairpin intronsUPRUTRX-box binding protein 1XBP1activating transcription factor 6endoplasmic reticulumendoplasmic reticulum stress response elementisoproterenolmiR-702mmu-miR-702mouse microRNA-702unfolded protein responseuntranslated regions

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