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Decrease in RNase HII and Accumulation of lncRNAs/DNA Hybrids: A Causal Implication in Psoriasis?

Ecmel Mehmetbeyoglu1,2, Leila Kianmehr3, Murat Borlu4

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Summary
This summary is machine-generated.

Psoriasis patients show increased levels of DNA-RNA hybrids, including Telomeric Repeat containing RNA (TERRA), in skin and blood. Reduced Ribonuclease HII (RNase-HII) activity may contribute to genomic instability and skin lesions in psoriasis.

Keywords:
RNA–DNA hybridRNase HIITERRAcancercentromeresepigeneticsnon-coding RNAspsoriasistelomere length

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Area of Science:

  • Molecular Biology
  • Genetics
  • Dermatology

Background:

  • Short telomeres and genomic instability are hallmarks of aging, cancer, and psoriasis.
  • Telomeric Repeat containing RNA (TERRA) levels are linked to telomere length and genomic instability.
  • Psoriasis involves epidermal keratinocyte dysfunction and altered telomerase activity.

Purpose of the Study:

  • To investigate the role of DNA-RNA hybrids and non-coding RNAs in psoriasis pathogenesis.
  • To explore the correlation between non-coding RNA levels, Ribonuclease HII (RNase-HII) activity, and psoriasis severity.
  • To assess the potential of RNase-HII as a prognostic marker for psoriasis.

Main Methods:

  • Fractionation of skin and blood samples to isolate RNA-DNA hybrid structures (R-loops).
  • Quantification of TERRA, non-telomeric TERRA, and centromeric transcripts.
  • Analysis of Ribonuclease HII (RNase-HII) transcript levels.

Main Results:

  • Elevated levels of TERRA at chromosome ends were observed in psoriasis patients' blood and skin.
  • Accumulation of non-telomeric TERRA and centromeric transcripts was evidenced in psoriasis.
  • Increased DNA-RNA hybrids correlated with decreased RNase-HII transcript levels.

Conclusions:

  • Unresolved DNA-RNA hybrids, potentially due to reduced RNase-HII, may weaken DNA and cause skin lesions in psoriasis.
  • RNase-HII plays a crucial role in maintaining genome stability and epigenome regulation.
  • RNase-HII transcript levels could serve as a prognostic marker for psoriasis patients.