tRNA m1A modification promotes benign prostatic hyperplasia through translational regulation of the TGF-β pathway [Ribo-seq]

Although global hypermethylation has been implicated in BPH pathogenesis, the specific role of N1-methyladenosine (m1A) tRNA modifications remains unclear. Here, we find that RNA m1A modification and its methyltransferase TRMT61A were significantly upregulated in BPH tissues.

Impaired m1A tRNA modification upon TRMT61A depletion resulted in decreased cell proliferation and contraction, as well as induced cell cycle arrest and apoptosis in prostate cells both in vitro and in vivo. Mechanistically, TRMT61A knockdown decreased m1A-modified tRNAs, impairing global translation and altering translational efficiency of specific genes. Moreover, ribosome profiling and RNA sequencing revealed that genes with reduced translational efficiency upon TRMT61A depletion were enriched in the TGF-β signaling pathway, including TGFβR1, INHBA, SMAD2, FST, and ID2.