Fig. 5

Ψ deposition mechanisms and pathological implications in cancer. a Schematic illustration of RNA-dependent pseudouridylation mechanisms. Substrate recognition is achieved by sequence and structure homology of the substrate with the structural stems and loops formed by box H/ACA small nucleolar RNAs (snoRNA). Dyskerin (DKC1) is the catalytic unit and non-histone protein 2 (Nhp2), nucleolar protein 10 (Nop10) and glycine-arginine-rich protein 1 (Gar1) are regulatory units. The RNA substrate is represented in green. b Illustration of RNA-independent pseudouridylation mechanisms. Substrate recognition and catalysis are performed by one single pseudouridine synthases (PUS) (blue). c Representative scheme illustrating the target specificity for each pseudouridine synthases. The fate of each modified RNA is also illustrated with orange arrows. Pseudouridylated RNAs may be also recognised by still unknown readers (?). d Altered expression of pseudouridine synthases can lead to cancer. For example, reduced expression of DKC1 induces a reduction of pseudouridylation in TERC and rRNA, leading to dysfunctional TERC and rRNA and increasing tumourigenesis. e In glioma, An increased expression of DKC1 can lead to an increased Ψ deposition on rRNA, snRNA and TERC, and thus promoting cancer cell growth and migration. f PUS7 decreased expression leads to hypomodified tRNA-derived fragments, leading to increased self-renewal and survival in bone marrow mononuclear cells, promoting tumourigenesis. Red arrows indicate an increase and blue arrows a decrease of processes or enzymes