On March 15th, the journal "Science" online published a significant breakthrough in the research of spliceosome structure and mechanism, titled "Structural Basis for Fully Assembled Minor Spliceosome Bound to U12-Type Intron." This achievement stems from the collaborative efforts of the team led by Dr. Wan Ruixue, a specially appointed researcher at Westlake University, and the team led by Professor Shi Yigong, Chair of Structural Biology. The first author of this research is Dr. Bai Rui, an associate researcher at Westlake University.
Title: High-Resolution 3D Structure of Fully Assembled Minor Spliceosome Revealed
The image provided showcases the three-dimensional structure of the fully assembled minor spliceosome. Image courtesy of the research team.
If we were to liken each person's genes to a grand screenplay, then RNA splicing would be akin to a magical wizard who deftly wields a wand, snipping away "invalid" genetic information and splicing in "valid" information to ultimately piece together a complete life's screenplay. And in this magical act, the spliceosome plays the pivotal role — composed primarily of hundreds of proteins and five small nuclear RNAs (snRNAs). Discovered relatively late and existing in low quantities within cells — comprising only 1/100th of all spliceosomes — these spliceosomes are termed minor spliceosomes, also known as U12-type spliceosomes; whereas the more abundant spliceosomes are termed major spliceosomes, or U2-type spliceosomes.
In 2021, the research team led by Wan Ruixue & Shi Yigong published their findings related to minor spliceosomes for the first time in the journal "Science". This time, the team reported the high-resolution three-dimensional structure of the fully assembled minor spliceosome, showcasing the critical conformational changes during the assembly process on U12-type introns — termed the pre-catalytic spliceosome precursor, defined as the "pre-B complex"), resolving and identifying 56 proteins and 6 RNAs, including pre-mRNA and five snRNAs, with an overall resolution of up to 3.3 angstroms.
For the first time, this structure revealed all five types of snRNPs comprising the minor spliceosome, namely U11, U12, U4atac, U6atac, and U5 snRNPs, unveiling the molecular mechanism of how the minor spliceosome recognizes the 5' splice site on U12-type introns during the assembly process. This study addresses the crucial question of how the 5' splice site gradually transitions into the active site during spliceosome activation. By comparing the structure of minor spliceosomes with that of major spliceosomes, the study also analyzes the structural basis of U2-type and U12-type intron recognition, proposing a model for how major and minor spliceosomes distinguish splice sites and correctly complete assembly at the molecular level.
For more information on the related paper, please visit: Science Article Link
