Targeted blocking of gene splicing can dysregulate intron-embedded primary microRNAs.

ABSTRACT: Addressing whether antisense oligonucleotides (ASOs)-based targeting of genes embedded with intronic noncoding RNAs (ncRNAs) affects the expression and function of intronic ncRNAs is crucial to the success of ASOs in clinical trials. While studying zebrafish posterior pituitary development-an important neuroendocrine interface-we found that an ASO targeting the slit3 splice site, but not the translation start site, disrupts pituitary axonal morphogenesis. In addition to altered slit3 splicing, we observed increased expression of slit3, its intron-embedded microRNA mir-218a-1, its longest intron, and the paralogous slit2 gene. The ASO-induced phenotype does not occur when mature mir-218a-1 is blocked by an ASO or in mir-218a-1^-/- mutants, or when the splicing of the exon immediat

SUBMITTER: Ali MH 

PROVIDER: S-EPMC12910030 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature