Oct 2026· Science Advances· Vol 12· 0 citations· 50 references
Medicine
Abstract
Ribosomal RNA modification enzymes increase cellular fitness, but it’s little known whether this benefit arises from rRNA modification or a chaperone function of the modification enzyme. Here, we show that E. coli methyltransferase RsmB chaperones the initial recruitment of ribosomal proteins to the 16S 3′ domain rRNA, a key step in assembly of the 30S subunit. Real-time single-molecule assembly experiments show that the RsmB product, 16S m5C967, has little effect on the rRNA affinity for ribosomal proteins. Instead, RsmB facilitates stable recruitment of primary protein uS7 during transcription while blocking the addition of secondary protein uS19. Completion of the methyltransferase cycle promotes RsmB release, allowing assembly to continue. Dimethyl sulfate footprinting of trapped RsmB-rRNA complexes revealed that RsmB restructures a critical rRNA helix junction. Our results illustrate how an RNA modification enzyme favors the proper sequence of protein addition by temporarily reshaping the energy landscape of co-transcriptional rRNA folding.
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It is demonstrated that linker-free PROTACs can outperform traditional designs, marking a paradigm shift in PROTAC development for targeted protein degradation.
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