biostudies-literatureKapral THAustrian Science Fund FWFUniversity of ViennaNational Natural Science Foundation of ChinaVolkswagenStiftung LIFENational Key Research and Development Plan of ChinaBeijing Advanced Innovation Center for Structural BiologyBio-Computing Platform of China National Center for Protein Sciences Beijing9984-9999https://www.ebi.ac.uk/biostudies/studies/S-EPMC9508846biostudies-literatureUnknown50(17)Autogenous interactions between mRNAs and the proteins they encode are implicated in cellular feedback-loop regulation, but their extent and mechanistic foundation are unclear. It was recently hypothesized that such interactions may be common, reflecting the role of intrinsic nucleobase-amino acid affinities in shaping the genetic code's structure. Here we analyze a comprehensive set of CLIP-seq experiments involving multiple protocols and report on widespread autogenous interactions across different organisms. Specifically, 230 of 341 (67%) studied RNA-binding proteins (RBPs) interact with their own mRNAs, with a heavy enrichment among high-confidence hits and a preference for coding sequence binding. We account for different confounding variables, including physical (overexpression and pNucleic acids researchWidespread autogenous mRNA-protein interactions detected by CLIP-seq.PMC950884631522030P 305502016YFA05008033177146198187P 30680-B21Lu ZJKapral THZhao WZagrovic BFarnhammer FfalseWidespread autogenous mRNA-protein interactions detected by CLIP-seq.Autogenous interactions between mRNAs and the proteins they encode are implicated in cellular feedback-loop regulation, but their extent and mechanistic foundation are unclear. It was recently hypothesized that such interactions may be common, reflecting the role of intrinsic nucleobase-amino acid affinities in shaping the genetic code's structure. Here we analyze a comprehensive set of CLIP-seq experiments involving multiple protocols and report on widespread autogenous interactions across different organisms. Specifically, 230 of 341 (67%) studied RNA-binding proteins (RBPs) interact with their own mRNAs, with a heavy enrichment among high-confidence hits and a preference for coding sequence binding. We account for different confounding variables, including physical (overexpression and p2022-01-01T00:00:00Z2022 Sep2025-04-18T20:57:36.365Z2025-04-07T08:55:41.4ZS-EPMC95088463610777910.1093/nar/gkac756