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Relationships between PROMPT and gene expression.

Marta Lloret-Llinares1,2, Christophe K Mapendano1,3,2, Lasse H Martlev1,4

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Most mammalian genes produce promoter upstream transcripts (PROMPTs) that are rapidly degraded. However, some PROMPTs may regulate gene activity, particularly during DNA damage response (DDR).

Keywords:
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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Biology

Background:

  • Most mammalian protein-coding gene promoters are divergent, producing promoter upstream transcripts (PROMPTs) in the opposite direction of mRNA.
  • PROMPTs are typically degraded by the RNA exosome, obscuring their potential functions.
  • Altered PROMPT levels during DNA damage response (DDR) suggest a regulatory role for a subset of these transcripts.

Purpose of the Study:

  • To investigate the potential regulatory role of PROMPTs.
  • To analyze the effects of manipulating PROMPT levels on neighboring gene activity.

Main Methods:

  • Depletion of the RNA exosome to increase PROMPT levels.
  • UV treatment to induce DNA damage response and alter PROMPT levels.
  • Analysis of promoter binding factors (TFIIB, TBP) and DNA methylation (DNMT3B) for CTSZ and DAP genes.

Main Results:

  • Accumulation of PROMPTs led to decreased binding of TFIIB and TBP at the CTSZ and DAP promoters.
  • Increased DNA methylation and recruitment of DNMT3B were observed with elevated PROMPT levels.
  • A general correlation between increased PROMPT levels and decreased gene activity was not found.

Conclusions:

  • Some gene promoters may utilize divergent transcript production for regulatory purposes.
  • PROMPT accumulation can influence promoter binding and DNA methylation, suggesting a role in gene regulation under specific conditions.