Corticotropin (ACTH) regulates alternative RNA splicing in y1 mouse adrenocortical tumor cells

• ACTH decreased levels of several transcripts with functions in alternative splicing.
• ACTH stimulated exon-skipping at Gnas, Cd151, and Dab2.
• ACTH stimulated exon-inclusion at two sites within Tia1.
• ACTH-regulated alternative splicing may shape the adrenal transcription landscape.

The stimulatory effect of ACTH on gene expression is well documented and is thought to be a major mechanism by which ACTH maintains the functional and structural integrity of the gland. Previously, we showed that ACTH regulates the accumulation of over 1200 transcripts in Y1 adrenal cells, including a cluster with functions in alternative splicing of RNA. On this basis, we postulated that some of the effects of ACTH on the transcription landscape of Y1 cells are mediated by alternative splicing. In this study, we demonstrate that ACTH regulates the alternative splicing of four transcripts – Gnas, Cd151, Dab2 and Tia1. Inasmuch as alternative splicing potentially affects transcripts from more than two-thirds of the mouse genome, we suggest that these findings are representative of a genome-wide effect of ACTH that impacts on the mRNA and protein composition of the adrenal cortex.