Another secret of a molecular scissor that helps prevent cancer
Oeiras, 20th October 2025
Cells control the expression of their genes at different levels. One strategy is to degrade the molecules that serve as intermediates between the information contained in DNA and the proteins that act on it, the messenger RNAs. There are several other types of RNAs with multiple functions in the cells. This entire process is highly regulated and has a precise quality control mechanism: RNA molecules are processed into mature forms, and those that are defective are marked for destruction. Ribonucleases (RNases) cleave the RNA into pieces to mature the RNAs or to degrade them for recycling.
Dis3L2, one of those RNases or “molecular scissors”, has a particular taste: it prefers RNA molecules with a tail of uridines (U), one of the building blocks of RNA, instead of the typical tail of adenines (A). Researchers believe that this tail of Us tags RNAs for fast removal by Dis3L2, including in stem and cancer cells. In fact, defects in Dis3L2 are associated with diseases, including colorectal cancer and hepatocellular carcinoma, and severe overgrowth disorders like Perlman's Syndrome.
In a new study, researchers from ITQB NOVA’s Control of Gene Expression Laboratory, led by Cecília M. Arraiano, in collaboration with Ankur Garg and Leemor Joshua-Tor from Cold Spring Harbour Laboratory, studied the activity of several versions of Dis3L2 RNase from fission yeast and determined its crystal structure when bound to a U-tailed RNA, providing new insights into how it degrades double-stranded RNA. This work was led by ITQB NOVA researcher Sandra C. Viegas, and was now published in the Journal RNA, from RNA Society.
“The crystal structure of Dis3L2 bound to an RNA substrate unveils the enzyme’s strategy for recognizing and degrading the RNA. After an extensive mutational analysis of this RNase, we discovered that changing a single residue of Dis3L2 disrupts its ability to degrade structured RNAs, highlighting a key determinant of its mechanism”, explain Rute G. Matos and Susana M. Costa, both researchers at ITQB NOVA and co-first authors of the study.
ITQB NOVA researchers Rute G. Matos, Susana M. Costa, Cecília M. Arraino, and Sandra C. Viegas (from left to right).
Original paper:
RNA Journal | doi:10.1261/rna.080685.125
Structural and mechanistic insights into Dis3L2–mediated degradation of structured RNA
Rute G. Matos, Ankur Garg, Susana M. Costa, Patrícia Pereira, Cecília M. Arraiano, Leemor Joshua-Tor and Sandra C. Viegas
