tRNA-splicing endonuclease subunit 15 (TSEN15)

tRNA-splicing endonuclease subunit 15 (TSEN15) is a critical non-catalytic component of the heterotetrameric tRNA-splicing endonuclease complex, which also includes TSEN2, TSEN34, and TSEN54. This complex is responsible for identifying and cleaving introns from precursor transfer RNAs (pre-tRNAs), a fundamental step in the maturation of functional tRNAs required for protein synthesis. Mutations in the TSEN15 gene are specifically linked to Pontocerebellar Hypoplasia type 2F (PCH2F), a severe autosomal recessive neurodevelopmental disorder characterized by microcephaly, cerebellar hypoplasia, and profound developmental delay. The mRNA 3' untranslated region (UTR) of TSEN15 serves as a regulatory hub, containing binding sites for microRNAs and RNA-binding proteins that control the stability and translation efficiency of the transcript. While no drugs are currently approved for this target, the 3' UTR is an emerging focus for antisense oligonucleotide (ASO) therapies designed to increase TSEN15 protein levels by blocking inhibitory regulatory elements, thereby potentially restoring TSEN complex function in patients with loss-of-function mutations.

Other names

SEN15tRNA-splicing endonuclease subunit Sen15C1orf19tRNA-intron endonuclease Sen15

Modulation of mRNA stability or translation (potential via antisense oligonucleotides targeting the 3' UTR)