The RNA secondary structure of androgen receptor-FL and V7 transcripts reveals novel regulatory regions

Warren B Rouse1, Van S Tompkins1, Collin A O'Leary1,2

  • 1Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA.

Nucleic Acids Research
|March 30, 2024
PubMed

Insights

Androgen receptor (AR) mRNA structure impacts its regulation. This study reveals novel RNA structures in AR isoforms, including a 5'UTR stem loop interacting with PCBP2, offering new insights into AR expression control.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The androgen receptor (AR) is crucial for cell growth and differentiation.
  • AR dysregulation is implicated in diseases like prostate cancer, often at the RNA level.
  • Post-transcriptional regulation of AR mRNA, especially RNA secondary structure, remains poorly understood.

Purpose of the Study:

  • To comprehensively analyze the secondary structure of androgen receptor (AR) mRNA.
  • To investigate the structural landscape and dynamics of full-length (AR-FL) and truncated (AR-V7) AR isoforms.
  • To identify functionally significant RNA structures within AR mRNA, particularly in untranslated regions.

Main Methods:

  • Utilized in-cell RNA secondary structure probing (targeted DMS-MaPseq).
  • Employed computational predictions to analyze AR mRNA structural features.
  • Conducted in-cell assays to assess the functional relevance of identified structures in AR-FL.

Main Results:

  • Characterized the static structure and conformational dynamics of AR-FL and AR-V7 mRNA.
  • Identified functionally relevant structures in the 5' and 3' untranslated regions (UTRs) of AR-FL.
  • Discovered a conserved 5'UTR stem-loop in AR-FL that binds Poly(RC) Binding Protein 2 (PCBP2).

Conclusions:

  • Novel RNA secondary structures play a significant role in regulating AR expression.
  • The identified AR mRNA structures and interactions provide new targets for understanding AR dysregulation.
  • This research elucidates previously unknown mechanisms of AR post-transcriptional control.

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