Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2021 Jun 2;29(6):1940-1942.
doi: 10.1016/j.ymthe.2021.04.032. Epub 2021 May 12.

Therapeutic targeting of RNA-binding protein by RNA-PROTAC

Xinyi Li  1 , Wenchen Pu  2 , Song Chen  3 , Yong Peng  4
Affiliations
Comment

Therapeutic targeting of RNA-binding protein by RNA-PROTAC

Xinyi Li et al. Mol Ther. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Figure 1
Figure 1
The mechanism and chemistry of peptide/small molecule-based PROTACs and RNA-PROTAC (A) PROTACs selectively degrade pathogenic proteins based on the ubiquitin-proteasome system that consists of specific enzymes (ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin ligase E3) modifying proteins with ubiquitin and 26S proteasomes degrading the ubiquitin-tagged proteins. Conventional PROTAC contains a small-molecule or peptidic ligand for the protein of interest (POI), a ligand of E3 ligase, and a linker connecting the latter two. RNA-PROTAC utilizes an oligoribonucleotide to recognize an RNA-binding protein (RBP, for example, Lin28) based on an endogenous RNA-protein interaction, thereby enhancing the degradation of the RBP. (B) Given the chemical structure of the moiety that recognizes the POI, PROTACs can be peptide-based, small molecule-based, and/or nucleotide-based. The graphics show the chemical structures of the peptide-based STAT3 PROTAC SD36, the small molecule-based BRAFV600E PROTAC P4B, and the Lin28 RNA-PROTAC ORN3P1.
See this image and copyright information in PMC

Comment on

  • RNA-PROTACs: Degraders of RNA-Binding Proteins.
    Ghidini A, Cléry A, Halloy F, Allain FHT, Hall J. Ghidini A, et al. Angew Chem Int Ed Engl. 2021 Feb 8;60(6):3163-3169. doi: 10.1002/anie.202012330. Epub 2020 Dec 10. Angew Chem Int Ed Engl. 2021. PMID: 33108679 Free PMC article.

References

    1. Ghidini A., Cléry A., Halloy F., Allain F.H.T., Hall J. RNA-PROTACs: degraders of RNA-binding proteins. Angew. Chem. Int. Ed. Engl. 2021;60:3163–3169. - PMC - PubMed
    1. Harrigan J.A., Jacq X., Martin N.M., Jackson S.P. Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat. Rev. Drug Discov. 2018;17:57–78. - PMC - PubMed
    1. Burslem G.M., Crews C.M. Proteolysis-targeting chimeras as therapeutics and tools for biological discovery. Cell. 2020;181:102–114. - PMC - PubMed
    1. Lai A.C., Crews C.M. Induced protein degradation: an emerging drug discovery paradigm. Nat. Rev. Drug Discov. 2017;16:101–114. - PMC - PubMed
    1. Schapira M., Calabrese M.F., Bullock A.N., Crews C.M. Targeted protein degradation: expanding the toolbox. Nat. Rev. Drug Discov. 2019;18:949–963. - PubMed

Publication types

LinkOut - more resources