Led by Professor Magda Konarska from the International Research Agenda ReMedy and University of Warsaw’s Centre of New Technologies, the research group described its research findings in the Molecular Cell journal. The researchers provided a discussion of the changes in the catalytic centre of a spliceosome. Also, they explained some aspects of splicing catalysis and suggested methods to regulate this process.
Splicing is the process of joining together genes. It involves removing non-coding regions (introns) from pre-mRNA and joining together coding regions (exons). Splicing errors may have an adverse effect on cell metabolism, apoptosis and the cell cycle. In some cases, they may also trigger neoplastic development.
The research presented in the paper showed that the catalythic centre of a spliceosome, comprising RNA molecules, underwent significant rearrangements that had not been observed before using high-resolution cryo-EM techniques. In all the known cryo-EM structures of the spliceosome, the catalythic centre remained identical at all stages of the reaction. Using yeast genetics and bioinformatic methods, the research group led by Professor Konarska proved that significant changes had occurred in the active centre. Moreover, their research showed that changes in the catalythic centre’s stability affected splicing efficiency and, consequently, alternative splicing regulation.
The research presented in the publication was conducted as part of the International Research Agenda ReMedy – Regenerative Mechanisms for Health. Operating under the University of Warsaw’s Centre of New Technologies, ReMedy aims to provide new insights into cellular processes and cellular stress responses to help develop more effective treatments for neurodegenerative and neoplastic diseases.
Led by Professor Agnieszka Chacińska and Professor Magdy Konarska, the project received more than PLN 35 million in funding for a period of five years. The Foundation for Polish Science has been implementing the International Research Agendas Programme since November 2015 based on Smart Growth Operational Programme (SG OP) funding. The Programme aims to facilitate the establishment in Poland of specialised research centres that conduct globally competitive research.
In the picture: Professor Agnieszka Chacińska and Professor Magda Konarska / picture by OneHD