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Biochemistry

Cancer target binds RNA and its mirror image

Degradation-resistant l-RNA could be used to develop anticancer therapeutics

by Cici Zhang
October 13, 2018 | APPEARED IN VOLUME 96, ISSUE 41

 

09641-scicon11-prc2cxd.jpg
Credit: Jonathan Sczepanski/PyMol/RCSB
The PRC2 protein is involved in gene silencing and cancer biology.

As chiral molecules, nucleic acids can exist in enantiomeric forms. Although l-nucleic acids aren’t found in nature, they could lead to development of new drugs that avoid degradation and immune response after they enter the human body. A team led by Jonathan Sczepanski of Texas A&M University reports the first example of a native RNA-binding protein that is capable of recognizing l-RNA (Chem. Commun. 2018, DOI: 10.1039/C8CC07433J). The protein, Polycomb Repressive Complex 2 (PRC2), is involved in epigenetic silencing of genes and cancer biology, and it is known to bind native d-RNA promiscuously. When the researchers mixed the protein with natural d-RNA and unnatural l-RNA, they found that the promiscuity of PRC2 extends to chirality: Both enantiomers bound competitively to the same site. The study also showed that the enantiomers displayed similar affinity for PRC2. Given that RNA has been shown to inhibit PRC2’s activity by preventing substrate binding, Sczepanski says these results suggest that degradation-resistant l-RNA could be used to develop a novel class of PRC2 inhibitors to unsilence tumor suppressor genes and work as anticancer compounds.

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