====== NSUN5 ======


Tumors have aberrant [[proteome]]s that often do not match their corresponding [[transcriptome]] profiles. One possible cause of this discrepancy is the existence of aberrant [[RNA]] modification landscapes in the so-called [[epitranscriptome]]. 

Janin et al. reported that human [[glioma cell]]s undergo [[DNA methylation]]-associated epigenetic silencing of NSUN5, a candidate RNA [[methyltransferase]] for [[5-methylcytosine]]. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. They also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S [[rRNA]] that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme [[NQO1]]. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease
((Janin M, Ortiz-Barahona V, de Moura MC, Martínez-Cardús A, Llinàs-Arias P,
Soler M, Nachmani D, Pelletier J, Schumann U, Calleja-Cervantes ME, Moran S, Guil
S, Bueno-Costa A, Piñeyro D, Perez-Salvia M, Rosselló-Tortella M, Piqué L,
Bech-Serra JJ, De La Torre C, Vidal A, Martínez-Iniesta M, Martín-Tejera JF,
Villanueva A, Arias A, Cuartas I, Aransay AM, La Madrid AM, Carcaboso AM,
Santa-Maria V, Mora J, Fernandez AF, Fraga MF, Aldecoa I, Pedrosa L, Graus F,
Vidal N, Martínez-Soler F, Tortosa A, Carrato C, Balañá C, Boudreau MW,
Hergenrother PJ, Kötter P, Entian KD, Hench J, Frank S, Mansouri S, Zadeh G, Dans
PD, Orozco M, Thomas G, Blanco S, Seoane J, Preiss T, Pandolfi PP, Esteller M.
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to
drive a stress adaptive translational program. Acta Neuropathol. 2019 Aug 19.
doi: 10.1007/s00401-019-02062-4. [Epub ahead of print] PubMed PMID: 31428936.
)).