2025/05/20 by Tahnee Mackensen, Manuel Irimia · 1 voice
Biochemistry, Genetics and Molecular Biology · #RNA Research and Splicing #RNA and protein synthesis mechanisms #RNA modifications and cancer
paper · doi:10.1146/annurev-genom-121323-103648
openalex publication_date 2025/05/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
Over the last decade, a set of very short (3-51 nt) and highly conserved microexons have been found to crucially influence a set of diverse protein functions and interactions. Advancements in RNA sequencing and analysis pipelines have revealed an enrichment for the alternative splicing of microexons in a subset of tissues and cell types, especially across the central nervous system. Microexons are thought to fine-tune important developmental processes such as synaptogenesis by preserving the protein's reading frame upon inclusion. Dysregulation of microexon splicing has been linked to several neurological conditions, including autism spectrum disorder and schizophrenia, as well as metabolic disorders like diabetes and various cancer types. This review discusses the expanding body of literature on the molecular and organismal consequences of microexon inclusion, emphasizing their evolutionary conservation, tissue specificity, and functional diversity. It also explores the potential for therapeutic interventions, including pharmacological modulation, on microexon splicing and splicing regulators like SRRM3 and SRRM4, offering perspectives on targeting diseases related to microexon misregulation. More research is needed to better understand similarities and differences between microexon functions across tissues, pathologies, and species.