Splicing activates transcription from weak promoters upstream of alternative exons.

ABSTRACT: Transcription and splicing are intrinsically coupled. Alternative splicing of internal exons can fine-tune gene expression through a recently described phenomenon called exon-mediated activation of transcription starts (EMATS). However, the association of this phenomenon with human diseases remains unknown. Here, we develop a strategy to activate gene expression through EMATS and demonstrate its potential for treatment of genetic diseases caused by loss of expression of essential genes. We first identified a catalog of human EMATS genes and provide a list of their pathological variants. To test if EMATS can be used to activate gene expression, we constructed stable cell lines expressing a splicing reporter based on the alternative splicing of motor neuron 2 (SMN2) gene. Using small molecul

SUBMITTER: Uriostegui-Arcos M 

PROVIDER: S-EPMC10256964 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature