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Study reveals blueprint of the most complex cell machine after a decade

Researchers have decoded one of the most complex molecular machines in human cells: the spliceosome. After more than ten years of work, a detailed blueprint provides new insights into gene regulation and opens up perspectives for innovative therapeutic approaches.

Cell machinery decoded: breakthrough for medicine

The spliceosome is a highly complex protein complex that plays a crucial role in the implementation of genetic information in every human cell. It processes RNA molecules by removing non-coding sections that do not contain direct information for building proteins and joining coding sequences together.

This process, called splicing, allows a cell to produce different protein variants from a single gene. The study of the Center for Genomic Regulation (CRG) in Barcelona is now revealing, for the first time after more than a decade of research, a precise blueprint for this cell machine. The spliceosome therefore consists of 150 different proteins and five small RNA molecules. Each component has specific tasks: some select RNA segments to remove, others ensure that cuts are made in the correct place, and still others act as “guardians” that prevent certain actions.

To decipher how it works, the researchers changed the expression of 305 spliceosome-related genes in human cancer cells. The effects were then observed genome-wide. CRG ICREA Research Professor Juan Valcárcel explains: “We now see it as a collection of many different flexible chisels that allow cells to shape genetic messages with a precision worthy of ancient marble sculptors.”

By understanding exactly what each part does, we can find entirely new ways to combat a wide range of diseases.” Research Professor Juan Valcárcel

Complex network

The study shows that the spliceosome is highly interconnected. A failure in one component can have far-reaching effects on the entire network. This could be particularly relevant for cancer research, as cancer cells often have changes in the spliceosome.

Dr. Malgorzata Rogalska, co-author of the study, says: “We are moving into an era in which we can fight diseases directly where genes are read.” The findings could lead to new therapeutic approaches, not only for cancer, but also for diseases of the nervous system and genetic diseases. The publicly available blueprint of the spliceosome allows researchers around the world to specifically search for errors in the splicing process and potentially develop new, more precise drugs that directly target gene regulation.