Psoriasis-Specific RNA Isoforms Identified by RNA-Seq Analysis of 173,446 Transcripts

Abstract

Background: Several studies have been published that investigated potential links between transcriptome changes and psoriasis using microarrays and RNA-seq technologies, but no previous study has analyzed expression profile of alternatively spliced transcripts in psoriasis.

Objectives: Identification of potential alternatively spliced RNA isoforms with disease-specific expression profile.

Methods: Using our published RNA sequencing data from lesional psoriatic (LP), non-lesional psoriatic (NLP), and normal control skin (C), we analyzed the differential expression of RNA splicing variants. LP sample was compared with NLP, as was LP with C and NLP with C.

Results: Transcript-based annotation analyzed 173,446 transcripts (RNA isoforms), and around 9,000 transcripts were identified as differentially expressed between study groups. Several previously undescribed RNA variants were found. For instance, transcript ETV3_3 (ENST00000326786) was significantly downregulated in LP and NLP skin. ETV3 is a transcriptional repressor that contributes to the downstream anti-inflammatory effects of IL-10. We also identified diseases-specific transcripts (S100A7A, IL36RN_4, and IL36G_3) of genes already recognized to be involved in inflammation and immune response.

Conclusion: Psoriasis is characterized by significant differences in the expression of RNA alternative isoforms. Description of these new isoforms improves our knowledge about this complex disease.

Keywords: RNA sequencing; psoriasis; transcript expression profiling; transcriptome.

Figure 1

Heatmap of the RNA-seq expression data for the 50 transcripts with the smallest FDR values (LP–C comparison) illustrating differences in transcriptional profiles. The violet bar denotes non-lesional skin samples, the green bar controls, and the red bar lesional samples.

Figure 2

Box plots illustrating some of the most differentially expressed transcripts between the LP and C samples. ETV3_3 and NLK_6 were highly expressed in control skin but downregulated in lesional and non-lesional skin. The other genes in the figures were all upregulated in the psoriatic samples, but less so in non-lesional skin. Abbreviations in the X-axis are LP, lesional, NLP, non-lesional, and C, control.

Figure 3

RT-PCR results for four different RNA isoforms (A–D) and a comparison between paired LP and NLP samples. RNA levels of individual genes (A–D are ETV3_3, S100A7A_2, IL36RN_4 and IL36G_3) are expressed relative level to the housekeeper gene. Statistical significance for the paired t-tests is designated as *, a p-value less than 0.05 and ***, a p-value less than 0.001.