{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Chunkit Kwok"],"species":["Homo Sapiens"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0010270000"],"submitter_email":["ckkwok42@cityu.edu.hk"],"submitter_affiliation":["City University of Hong Kong"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"pubmed_abstract":["RNA G-quadruplexes (rG4s) are non-canonical secondary nucleic acid structures found in the transcriptome. They play crucial roles in gene regulation by interacting with G4-binding proteins (G4BPs) in cells. rG4-G4BP complexes have been associated with human diseases, making them important targets for drug development. Generating innovative tools to disrupt rG4-G4BP interactions will provide a unique opportunity to explore new biological mechanisms and potentially treat related diseases. Here, we have rationally designed and developed a series of rG4-based proteolytic targeting chimeras (rG4-PROTACs) aimed at degrading G4BPs, such as DHX36, a specific G4BP that regulates gene expression by binding to and unraveling rG4 structures in messenger RNAs (mRNAs). Our comprehensive data and systematic analysis reveals that rG4-PROTACs predominantly and selectively degrade DHX36 through a proteosome-dependent mechanism, which promotes the formation of the rG4 structure in mRNA, leading to the translation inhibition of rG4-containing transcripts. Notably, rG4-PROTACs inhibit rG4-mediated APP protein expression, and impact the proliferative capacity of skeletal muscle stem cells by negatively regulating Gnai2 protein expression. In summary, rG4-PROTACs provide a new avenue to understand rG4-G4BP interactions and the biological implications of dysregulated G4BPs, promoting the development of PROTACs technology based on the non-canonical structure of nucleic acids."],"pubmed_title":["RNA G-quadruplex structure-based PROTACs for targeted DHX36 protein degradation and gene activity modulation in mammalian cells."],"pubmed_authors":["Zhang Kun K, Nie Qichang Q, Li Maolin M, Chen Xiaona X, Zhong Liting L, Dai Tianle T, Guo Xiaofan X, Zhao Haizhou H, Lau Terrence Chi-Kong TC, Wang Huating H, Chen Shuo-Bin SB, Kwok Chun Kit CK"],"additional_accession":[]},"is_claimable":false,"name":"Proteomic analysis of rG4_A selectively degraded proteins through the proteasome","description":"To explore the effects of rG4-PROTACs on the whole proteome, Hela cells were treated with blank (empty transfection control), rG4 mut_A, rG4_A, or rG4_A plus MG132, and a proteomic analysis was included in the subproject","dates":{"publication":"Thu Nov 21 00:00:00 GMT 2024"},"accession":"PXD058113","cross_references":{"TAXONOMY":["9606"],"pubmed":["39883012"]}}