μ-Opioid receptor transcriptional variants in the murine forebrain and spinal cord

•The primary μ-opioid receptor transcript (Oprm1) in mouse contains a long 3′UTR.•The long Oprm1 3′UTR is ubiquitous in the murine central nervous system.•The variant shows high homology to the human primary OPRM1 transcript. Oprm1, the gene encoding the μ-opioid receptor, has multiple reported tran...

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Published in:Gene 2025-01, Vol.932, p.148890, Article 148890
Main Authors: Chrószcz, Magdalena, Hajto, Jacek, Misiołek, Klaudia, Szumiec, Łukasz, Ziemiańska, Magdalena, Radlicka-Borysewska, Anna, Borczyk, Małgorzata, Zięba, Mateusz, Gołda, Sławomir, Siwiec, Marcin, Ziółkowska, Barbara, Piechota, Marcin, Korostyński, Michał, Rodriguez Parkitna, Jan
Format: Article
Language:English
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Summary:•The primary μ-opioid receptor transcript (Oprm1) in mouse contains a long 3′UTR.•The long Oprm1 3′UTR is ubiquitous in the murine central nervous system.•The variant shows high homology to the human primary OPRM1 transcript. Oprm1, the gene encoding the μ-opioid receptor, has multiple reported transcripts, with a variable 3′ region and many alternative sequences encoding the C-terminus of the protein. The functional implications of this variability remain mostly unexplored, though a recurring notion is that it could be exploited by developing selective ligands with improved clinical profiles. Here, we comprehensively examined Oprm1 transcriptional variants in the murine central nervous system, using long-read RNAseq as well as spatial and single-cell transcriptomics. The results were validated with RNAscope in situ hybridization. We found a mismatch between transcripts annotated in the mouse genome (GRCm38/mm10) and the RNA-seq results. Sequencing data indicated that the primary Oprm1 transcript has a 3′ terminus located on chr10:6,860,027, which is ∼ 9.5 kilobases downstream of the longest annotated exon 4 end. Long-read sequencing confirmed that the final Oprm1 exon included a 10.2 kilobase long 3′ untranslated region, and the presence of the long variant was unambiguously confirmed using RNAscope in situ hybridization in the thalamus, striatum, cortex and spinal cord. Conversely, expression of the Oprm1 reference transcript or alternative transcripts of the Oprm1 gene was absent or close to the detection limit. Thus, the primary transcript of the Oprm1 mouse gene is a variant with a long 3′ untranslated region, which is homologous to the human OPRM1 primary transcript and encodes the same conserved C-terminal amino acid sequence.
ISSN:0378-1119
1879-0038
1879-0038
DOI:10.1016/j.gene.2024.148890