Spain: Researchers at the Centre for Genomic Regulation (CRG) in Barcelona have concluded the first detailed blueprint of the human spliceosome, a breakthrough that took over a decade. This complex molecular machine, reliable for editing genetic messages, influences the production of diverse protein variations from a single gene—a process essential to human biology but previously uncharted due to its complexity.
The spliceosome’s role is central: it edits RNA transcribed from DNA, deciding which protein versions are made by removing non-coding RNA segments and stitching together the coding ones. Errors in this process have been linked to diseases like cancer, neurodegenerative disorders, and genetic conditions. The CRG team’s blueprint unveils new insights into the spliceosome’s components, showing that each has highly specialized functions, some of which were unknown and unexploited in drug development until now.
Lead author and ICREA Research Professor Juan Valcarcel explained that, “This discovery reveals a level of complexity that can now inform targeted therapies for a range of diseases.” With new knowledge of each component’s role, researchers can design more precise drugs, offering fewer side effects.
Among the significant findings is the highly interconnected nature of the spliceosome, where disrupting a single component can trigger a domino effect across the network. By studying the SF3B1 spliceosome component—mutated in various cancers including leukemia, melanoma, and breast cancer—the researchers observed how targeting splicing machinery could lead to the self-destruction of cancer cells by pushing them beyond their limits for sustaining growth.
Dr. Valcarcel notes the potential of this research to revolutionize cancer therapies. Dr. Valcarcel stated that, “The spliceosome’s interconnected structure creates a unique vulnerability in cancer cells, presenting an ‘Achilles’ heel’ we can leverage to disrupt their growth.”
Beyond cancer, the blueprint’s release as a public resource is expected to accelerate treatment discovery for numerous diseases driven by splicing errors. Dr. Valcarcel highlights the impact, stating that this detailed map may broaden splicing therapies from rare diseases to more common conditions. Co-author Dr. Malgorzata Rogalska concluded that, “This blueprint paves the way for pioneering disease-modifying drugs that address issues at the genetic transcription level.”