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Recently Evolved Tumor Suppressor Transcript TP73-AS1 Functions as Sponge of Human-Specific miR-941.

Haiyang Hu1,2, Jian-Mei Liu3, Zhenyu Hu3

  • 1School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.

Molecular Biology and Evolution
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A newly discovered noncoding RNA, TP73-AS1, acts as a microRNA (miRNA) sponge for human-specific miR-941. This rapidly evolved interaction regulates genes involved in cell growth and cancer.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Evolutionary Biology

Background:

  • MicroRNA (miRNA) sponges are crucial for gene regulation, but few have been identified.
  • The TP73-AS1 transcript is a recently evolved noncoding RNA with tumor suppressor functions.

Purpose of the Study:

  • To investigate the function of TP73-AS1 as a potential miRNA sponge.
  • To explore the evolutionary origin and regulatory role of the TP73-AS1 and miR-941 interaction.

Main Methods:

  • Bioinformatic analysis of TP73-AS1 and miR-941 binding sites.
  • Transcriptome data analysis across various tissues.
  • In vitro experiments including wound-healing assays and Argonaute protein immunoprecipitation.

Main Results:

  • TP73-AS1 contains nine high-affinity binding sites for human-specific miR-941, forming an efficient sponge.
  • The miR-941 sponge region evolved rapidly in humans from a primate precursor.
  • Inverse correlation between TP73-AS1 and miR-941 expression in healthy and cancerous tissues, with miR-941 upregulated in tumors.

Conclusions:

  • The TP73-AS1/miR-941 system represents a rapidly evolved regulatory mechanism.
  • This interaction influences cell migration, proliferation, and tumorigenesis.
  • Highlights the significance of noncoding RNA evolution in human-specific regulatory pathways.