Decrease in Rnase HII and accumulation of lncRNAs/DNA hybrids: a causal implication in psoriasis?

Long functional non-coding RNAs (lncRNAs) have been in the limelight in aging research because short telomeres are associated with higher levels of TERRA (Telomeric Repeat containing RNA). The genomic instability caused in Immune-mediated inflammatory diseases (IMID) especially in patients with psoriasis, which lead to short telomeres in psoriasis lesions, is a mechanism leading to cell aging. Research on the fraction of TERRA in hybrid with DNA offers avenues for new strategies. Skin samples were fractionated to obtain the RNA associated with DNA as a R-loop structure. TERRA analysis was performed by RT-qPCR and RNA-seq analysis. The higher amount of TERRA levels attached with each chromosome end was found with psoriasis patients. The increased levels of TERRA linked with telomeres correlate with the decrease in the RNase-HII transcript which means the unresolved DNA/RNA hybrids may ultimately facilitate the formation of skin lesions. LncRNAs have multiple molecular functions, including the regulation of heterochromatin, which controls genome stability and epigenome shaping and may be used as a trans-generational prognostic marker in patients with psoriasis. The signal of the lncRNAs is higher as DNA/RNAs hybrid (R-Loop) in patients with psoriasis in lesional tissues and above all, already in non-lesional tissues; -lncRNAs such as TERRA are found at higher levels at the end of each chromosome in patients with psoriasis, resulting in telomeres shortening; - and more importantly the idea that higher levels of lncRNAs attached to the genome lead to phenotypic changes DNA-associated RNA molecules were purified form 7 skin biopsy samples (2 Lesional, 2 Non-lesional, and 3 Control). 10-100 ng of RNA after Dnase digestion were recovered and analyzed by high throughput sequencing on Illumina.