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tRNA pseudouridine synthase 10 (PUS10) is a pseudouridylate synthase enzyme that catalyzes the isomerization of specific uridine residues to pseudouridine in RNA, a modification critical for the proper folding, stability, and function of various RNAs, especially tRNAs[1][3][5]. PUS10 is unique among pseudouridine synthases in that it possesses a structurally distinct THUMP domain at its N-terminus, involved in RNA binding and substrate recognition[1][5]. In eukaryotes, PUS10 primarily modifies uridine at positions 54 and 55 in the TΨC loop of specific tRNAs[1][3]. Human PUS10 serves additional roles beyond tRNA modification: in the nucleus, a catalytically inactive isoform regulates the timing of tRNA modification, preventing premature modification by other synthases[3]. PUS10 also interacts directly with the nuclear microprocessor complex to facilitate the processing of primary miRNAs into mature forms, a function independent of its catalytic pseudouridylation activity[2][3]. During tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, nuclear PUS10 is cleaved by caspase-3 and translocates to the mitochondria, supporting mitochondrial membrane permeabilization and amplifying caspase-mediated cell death signaling[1][3]. PUS10 tends to promote cell proliferation and may participate in cancer cell survival and apoptosis regulation[2]. There is currently no known small molecule drug or clinical agent that directly targets PUS10, nor have biomarker or safety data specifically for PUS10-targeting therapies been reported in public sources[3]. Its disease associations are implied by functional studies in apoptosis and oncology and through genetic links in inflammation, but no direct diagnostic or therapeutic use is established[3]. In summary, PUS10 is a multifunctional RNA-modifying enzyme central to tRNA stability, miRNA maturation, and apoptosis signaling, representing an emerging node in the interface between RNA biology and cell fate decisions[1][2][3][5].
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