News

Published: 28 February 2025
 
The genetic information for protein synthesis, deposited in the DNA, is initially transcribed into a precursor mRNA, which not only contains the protein-encoding nucleotide sequence (called exons) but also interspersed non-coding segments (called introns). The spliceosome, a large molecular machine, assembles on exon-intron boundaries and catalyzes the removal of introns, resulting in mature mRNAs containing only the coding sequence for proteins. In their new study, the Hurt lab investigated spliceosome complexes that recognize and reject precursor mRNAs with faulty exon-intron boundaries, which if spliced could lead to defective proteins. They show that two so far poorly characterized quality control factors, DHX35 and GPATCH1, work together to cancel the splicing reaction and dissociate the precursor mRNA from the spliceosome. The study was carried out in collaboration with structural biologists from Shanghai.
 
Y. Li, P. Fischer, M. Wang, Q. Zhou, A. Song, R. Yuan, W. Meng, F. X. Chen, R. Lührmann, B. Lau, E. Hurt, J. Cheng: Structural insights into spliceosome fidelity: DHX35-GPATCH1-mediated rejection of aberrant splicing substrates. Cell Research 35, pages 296–308 (2025)
 
DOI: 10.1038/s41422-025-01084-w