Primate-specific adaptation of Ku protects transcriptomic integrity by suppressing Alu-mediated alternative splicing.

ABSTRACT: Accurate pre-mRNA splicing is essential for the transfer of genetic information but faces unique challenge in higher primates due to the massive expansion of intronic Alu elements^1-3. While studying Ku, the Ku70/Ku80 heterodimer best known for initiating non-homologous end-joining (NHEJ) by encircling DNA ends⁴, we discovered that Ku expression increased markedly during primate evolution in parallel with Alu expansion⁵. Ku binds double-stranded RNA (dsRNA) stem-loops, including those at the antisense Alu (asAlu) elements within introns⁵. Here, we show that Ku-depletion in human cells has a broad impact on splicing largely independent of cell-cycle states, NHEJ, or innate immune signaling, significantly affecting ~8-10% of quantifiable alternative

SUBMITTER: Yu T 

PROVIDER: S-EPMC12724504 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature