A recent study suggests that ribosome MARylation in cancers maintains proteostasis by reducing protein synthesis and preventing toxic protein aggregation. Mechanistically, NMNAT-2 is a cytosolic NAD+ synthase that supports the catalytic activity of PARP-16, which mediates ribosomal proteins MARylation. Ribosomal protein MARylation regulates polysomes assembly or function through 3′UTR stem-loop secondary structures in mRNAs, resulting in reduced protein synthesis and preventing toxic protein aggregation, thus supporting the growth of cancer cells during accelerated cell growth. When PARP-16 or NMNAT-2 is deleted, stem-loop element in the 3′UTRs of mRNAs increases polysome loading, enhances protein synthesis, promotes toxic protein aggregation, leading to inhibited cancer cell growth. Collectively, ribosome MARylation provide us an exciting and scientific direction for us to understand cancers.

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