tRNA splicing endonuclease subunit 15 (TSEN15) (TSEN15)

tRNA splicing endonuclease subunit 15 (TSEN15) is a protein-coding gene that produces an mRNA transcript essential for the assembly of the heterotetrameric tRNA splicing endonuclease complex. This complex, which also includes TSEN2, TSEN34, and TSEN54, is responsible for identifying and cleaving introns from precursor tRNA molecules, a vital step in the maturation of functional tRNAs (UniProt Q8WW01). While the TSEN complex is ubiquitously expressed, its function is particularly critical during embryonic brain development, specifically in the growth of the cerebellum and pons. Mutations in the TSEN15 gene lead to Pontocerebellar Hypoplasia type 2F (PCH2F), a rare autosomal recessive disorder characterized by severe microcephaly, motor impairment, and cognitive deficits (OMIM 614961). Currently, there are no approved pharmacological agents that directly target TSEN15 mRNA; however, it is a subject of intense research for potential gene replacement or RNA-modulating therapies. Therapeutic development faces significant challenges, including the need for precise delivery to the central nervous system and the risk of disrupting delicate RNA processing pathways. Monitoring TSEN15 mutation status and cerebellar morphology via neuroimaging serves as the primary method for diagnosing and tracking the progression of associated diseases.

Other names

SEN15C1orf19tRNA-intron endonuclease 15tRNA splicing endonuclease 15 homolog

Potential therapeutic strategies involve the use of antisense oligonucleotides (ASOs) or gene therapy to restore functional TSEN15 protein levels or correct splicing defects caused by mutations.