Hominoid SVA-lncRNA AK057321 targets human-specific SVA retrotransposons in SCN8A and CDK5RAP2 to initiate neuronal maturation.

ABSTRACT: SINE-VNTR-Alu (SVA) retrotransposons arose and expanded in the genome of hominoid primates concurrent with the slowing of brain maturation. We report genes with intronic SVA transposons are enriched for neurodevelopmental disease and transcribed into long non-coding SVA-lncRNAs. Human-specific SVAs in microcephaly CDK5RAP2 and epilepsy SCN8A gene introns repress their expression via transcription factor ZNF91 to delay neuronal maturation. Deleting the SVA in CDK5RAP2 initiates multi-dimensional and in SCN8A selective sodium current neuronal maturation by upregulating these genes. SVA-lncRNA AK057321 forms RNA:DNA heteroduplexes with the genomic SVAs and upregulates these genes to initiate neuronal maturation. SVA-lncRNA AK057321 also promotes species-specific cortex and cerebellum-enriched

SUBMITTER: Nadler MJS 

PROVIDER: S-EPMC10063665 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature