PMID- 25250214 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20140924 LR - 20211021 IS - 2167-8359 (Print) IS - 2167-8359 (Electronic) IS - 2167-8359 (Linking) VI - 2 DP - 2014 TI - Identification of a truncated splice variant of IL-18 receptor alpha in the human and rat, with evidence of wider evolutionary conservation. PG - e560 LID - 10.7717/peerj.560 [doi] LID - e560 AB - Interleukin-18 (IL-18) is a pro-inflammatory cytokine which stimulates activation of the nuclear factor kappa beta (NF-kappaB) pathway via interaction with the IL-18 receptor. The receptor itself is formed from a dimer of two subunits, with the ligand-binding IL-18Ralpha subunit being encoded by the IL18R1 gene. A splice variant of murine IL18r1, which has been previously described, is formed by transcription of an unspliced intron (forming a 'type II' IL18r1 transcript) and is predicted to encode a receptor with a truncated intracellular domain lacking the capacity to generate downstream signalling. In order to examine the relevance of this finding to human IL-18 function, we assessed the presence of a homologous transcript by reverse transcription-polymerase chain reaction (RT-PCR) in the human and rat as another common laboratory animal. We present evidence for type II IL18R1 transcripts in both species. While the mouse and rat transcripts are predicted to encode a truncated receptor with a novel 5 amino acid C-terminal domain, the human sequence is predicted to encode a truncated protein with a novel 22 amino acid sequence bearing resemblance to the 'Box 1' motif of the Toll/interleukin-1 receptor (TIR) domain, in a similar fashion to the inhibitory interleukin-1 receptor 2. Given that transcripts from these three species are all formed by inclusion of homologous unspliced intronic regions, an analysis of homologous introns across a wider array of 33 species with available IL18R1 gene records was performed, which suggests similar transcripts may encode truncated type II IL-18Ralpha subunits in other species. This splice variant may represent a conserved evolutionary mechanism for regulating IL-18 activity. FAU - Booker, Chris S AU - Booker CS AD - Centre for Neuroendocrinology, Department of Anatomy, University of Otago , Dunedin , New Zealand. FAU - Grattan, David R AU - Grattan DR AD - Centre for Neuroendocrinology, Department of Anatomy, University of Otago , Dunedin , New Zealand. LA - eng PT - Journal Article DEP - 20140911 PL - United States TA - PeerJ JT - PeerJ JID - 101603425 PMC - PMC4168765 OTO - NOTNLM OT - Comparative genomics OT - Interleukin-18 OT - Splice variant OT - Toll-like receptor EDAT- 2014/09/25 06:00 MHDA- 2014/09/25 06:01 PMCR- 2014/09/11 CRDT- 2014/09/25 06:00 PHST- 2014/05/31 00:00 [received] PHST- 2014/08/15 00:00 [accepted] PHST- 2014/09/25 06:00 [entrez] PHST- 2014/09/25 06:00 [pubmed] PHST- 2014/09/25 06:01 [medline] PHST- 2014/09/11 00:00 [pmc-release] AID - 560 [pii] AID - 10.7717/peerj.560 [doi] PST - epublish SO - PeerJ. 2014 Sep 11;2:e560. doi: 10.7717/peerj.560. eCollection 2014.