Abstract
Multiple classes of small RNAs (sRNAs) are expressed in the blood and are involved in the regulation of pivotal cellular processes. We aimed to elucidate the expression patterns and functional roles of sRNAs in the systemic response to intracranial aneurysm (IA) rupture. We used next-generation sequencing to analyze the expression of sRNAs in patients in the acute phase of IA rupture (first 72 h), in the chronic phase (3–15 months), and controls. The patterns of alterations in sRNA expression were analyzed in the context of clinically relevant information regarding the biological consequences of IA rupture. We identified 542 differentially expressed sRNAs (108 piRNAs, 99 rRNAs, 90 miRNAs, 43 scRNAs, 36 tRNAs, and 32 snoRNAs) among the studied groups with notable differences in upregulated and downregulated sRNAs between the groups and sRNAs categories. piRNAs and rRNAs showed a substantial decrease in RNA abundance that was sustained after IA rupture, whereas miRNAs were largely upregulated. Downregulated sRNA genes included piR-31080, piR-57947, 5S rRNA, LSU-rRNA, and SSU-rRNA s. Remarkable enrichment in the representation of transcription factor binding sites was revealed in genomic locations of the regulated sRNA. We found strong overrepresentation of glucocorticoid receptor, retinoid x receptor alpha, and estrogen receptor alpha binding sites at the locations of downregulated piRNAs, tRNAs, and rRNAs. This report, although preliminary and largely proof-of-concept, is the first to describe alterations in sRNAs abundance levels in response to IA rupture in humans. The obtained results indicate novel mechanisms that may constitute another level of control of the inflammatory response.Key messagesA total of 542 sRNAs were differentially expressed after aneurysmal SAH comparing with controlspiRNAs and rRNAs were upregulated and miRNAs were downregulated after IA ruptureThe regulated sRNA showed an enrichment in the representation of some transcription factor binding sitespiRNAs, tRNAs, and rRNAs showed an overrepresentation for GR, RXRA, and ERALPHA binding sites
Highlights
Intracranial aneurysm (IA) rupture results in many systemic effects and strongly influences immune system function
To investigate the specificity of the regulation patterns described, we compared the abundance of each sRNA class with a group of randomly selected, nonregulated sRNAs that included a similar number of sequences as the largest regulated group (n = 233, Fig. 2, Supplementary Table S2)
To the best of our knowledge, this report is the first to describe the effects of intracranial aneurysm (IA) rupture on sRNA expression in peripheral blood cells
Summary
Intracranial aneurysm (IA) rupture results in many systemic effects and strongly influences immune system function. RNAs (ncRNAs) play a crucial role in many pathological conditions According to their length, ncRNAs are divided into two large categories: long (> 200 bp) and small (< 200 bp) ncRNAs. Small ncRNAs (sncRNAs) are a highly heterogenic group comprising microRNAs (miRNAs), piwiinteracting RNAs (piRNAs), short interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), promoter-associated small RNAs (PASRs), transfer RNAs (tRNAs), and ribosomal RNAs (rRNAs). Small ncRNAs (sncRNAs) are a highly heterogenic group comprising microRNAs (miRNAs), piwiinteracting RNAs (piRNAs), short interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), promoter-associated small RNAs (PASRs), transfer RNAs (tRNAs), and ribosomal RNAs (rRNAs) These RNAs are regulatory molecules influencing gene transcription, translation, genome integrity preservation, and epigenetic regulation [5,6,7,8]
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