The study revealed the catalytic mechanism of the nuclease RNaseMRP

research by the Thunder team at the Institute of Precision Medicine of the Ninth People's Hospital, affiliated with Shanghai Jiao university school of medicine, reveals the molecular mechanisms of the processing of rRNA, a conservative and necessary type of nuclear enzyme RNaseMRP, in the etrophysics. The results were published online June 25 in Science.
RNaseMRP is a conservative RNA complex consisting of a non-coding RNA catalytic sub-base and nearly ten proteins present in all ebony organisms. It plays an important role in the maturation process of the rRNA presupposor of therna and in the regulation of cell cycles.
mutations in the RNA-based RNaseMRP RNA group led to severe developmental defects characterized by dwarfism, cartilage, and hair stunting. In composition and evolution, RNaseMRP is closely related to another conservative and necessary type of nuclear enzyme in the body, RNaseP. However, they have completely different substrate specificity and substrate recognition mechanism, and they are not functionally redundant. RNaseP catalytic substrates are primarily tRNA presymbodies, catalytic cutting pre-tRNA5'leader and thus promoting the maturation of tRNA. RNaseP identifies the acceptorstem structure of tRNA through the "doubleanchor" mechanism and is not sequence-specific.
Previously, the Thunder team analyzed the whole enzyme and its substrate structure of yeast, paleobacteria, and human source RNaseP, explained in detail the substrate recognition and catalytic mechanism of RNaseP, and provided new evolutionary insights into the nucleases that exist in all living things on This species. In this work, the Thunder team successfully extracted the RNase MRP complex from yeast and analyzed the high-resolution structure of RNaseMRP whole enzyme and compound with substrate, which clearly revealed how RNaseMRP was developed by RNaseP and obtained a new and different substrate specificity. In terms of substrate recognition, RNaseMRP abandons the dual anchoring mechanism used by RNaseP, but on the catalytic core, the dual magnesium ion SN2 catalytic reaction mechanism used by RNaseP is completely preserved.
a central and critical question: What determines the substrate specificity of RNaseMRP? Combined with the structure of RNaseMRP-substrate complex and in-body bio-chemical experiments, it is shown that several key protein substrates located around the RNase MRP substrate binding pockets are compared to the structures in RNaseP, which use completely different folding methods and give RNaseMRP different substrate specificity. Unlike RNase P, which catalyticizes the three-dimensional structural characteristics of the substrate tRNA preatural, it identifies only a short single-stranded RNA fragment and has a certain sequence specificity.
RNaseMRP's RNA catalytic sub-base and telomerase RNA sub-base are the only two widely accepted and validated non-coding RNA molecules in the nuclei of cells that are closely related to human genetic diseases, and this work provides a solid basis for understanding the catalytic and mutation-causing pathogenicity of RNaseMRP.
that the research was supported by the National Natural Science Foundation of China, the Shanghai Science and Technology Commission, the Shanghai Municipal Education Commission and the Shanghai High-level Local University Innovation Team. (Source: Huang Xin Wang Lijun, China Science Journal)
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