biostudies-literatureGallo CMNIA NIH HHSNCI NIH HHSNIGMS NIH HHS110318https://www.ebi.ac.uk/biostudies/studies/S-EPMC8978334biostudies-literatureUnknown114(2)Apolipoprotein E receptor 2 (Apoer2) is a synaptic receptor in the brain that binds disease-relevant ligand Apolipoprotein E (Apoe) and is highly alternatively spliced. We examined alternative splicing (AS) of conserved Apoer2 exons across vertebrate species and identified gain of exons in mammals encoding functional domains such as the cytoplasmic and furin inserts, and loss of an exon in primates encoding the eighth LDLa repeat, likely altering receptor surface levels and ligand-binding specificity. We utilized single molecule, long-read RNA sequencing to profile full-length Apoer2 isoforms and identified 68 and 48 unique full-length Apoer2 transcripts in the mouse and human cerebral cortex, respectively. Furthermore, we identified two exons encoding protein functional domains, the thirdGenomicsSingle molecule, long-read Apoer2 sequencing identifies conserved and species-specific splicing patterns.PMC8978334F31 AG069498R21 AG072433P30 CA045508T32 GM008541R01 AG059762Beffert UGallo CMHo ALabadorf ATfalseSingle molecule, long-read Apoer2 sequencing identifies conserved and species-specific splicing patterns.Apolipoprotein E receptor 2 (Apoer2) is a synaptic receptor in the brain that binds disease-relevant ligand Apolipoprotein E (Apoe) and is highly alternatively spliced. We examined alternative splicing (AS) of conserved Apoer2 exons across vertebrate species and identified gain of exons in mammals encoding functional domains such as the cytoplasmic and furin inserts, and loss of an exon in primates encoding the eighth LDLa repeat, likely altering receptor surface levels and ligand-binding specificity. We utilized single molecule, long-read RNA sequencing to profile full-length Apoer2 isoforms and identified 68 and 48 unique full-length Apoer2 transcripts in the mouse and human cerebral cortex, respectively. Furthermore, we identified two exons encoding protein functional domains, the third2022-01-01T00:00:00Z2022 Mar2025-04-04T08:54:14.668Z2025-04-04T08:54:14.668ZS-EPMC89783343519289310.1016/j.ygeno.2022.110318