New breakthrough: How filamentous fungi help with RNA cleavage!

New breakthrough: How filamentous fungi help with RNA cleavage!

On March 28, 2025, researchers at Heidelberg University, together with international partners, made significant progress in understanding RNA splicing. These processes are crucial for correct protein production and therefore for the vital functions of cells. The information needed to make proteins is stored in DNA and derived via messenger RNA (mRNA). During processing, the structure of the pre-mRNA, which contains both coding (exons) and non-coding parts (introns), is changed. University of Heidelberg reports, that this process – splicing – is crucial for the production of functional proteins.

During splicing, introns must be removed and exons rejoined together. A complex ensemble of molecules known as the spliceosome is responsible for this process. It consists of a combination of RNA and protein components, whose precise arrangement and function are of great importance for the accuracy of the splicing process. A team of Heidelberg biochemists and international structural biologists has now discovered that the spliceosome is able to recognize non-authentic splice sites.

Crucial discoveries about splicing proteins

In the study, which focused on the spliceosomes of the thermophilic filamentous fungusChaetomium thermophilumfocused, two proteins, GPATCH1 and DHX35, were identified as critical to the fidelity of the splicing process. The research shows, that GPATCH1 recognizes defective pre-mRNA and stops the spliceosome, while DHX35 removes inappropriate precursor mRNA. These mechanisms prevent the formation of defective proteins that could result from incorrect splicing.

The researchers in Heidelberg, Shanghai and Göttingen also analyzed the structure of spliceosomes in detail using cryo-electron microscopy (cryo-EM). The ctILS complex shows a high similarity to the corresponding structures inC. elegansand suggests that the fundamentals of splicing are conserved across different organisms. These findings expand knowledge of the molecular mechanisms of splicing and could have far-reaching implications for understanding diseases.

Importance of RNA splicing

RNA splicing is not only a fundamental biological process, but also plays a central role in medicine. How Microbe Notes explains, errors in splicing can lead to a variety of diseases, including cancer and neurodegenerative diseases. These procedures are particularly necessary in eukaryotic cells, while they do not occur in prokaryotic cells. Introns must be removed from the pre-mRNA to join the exons, which are coding sections and enable protein synthesis.

Alternative splicing also allows the production of different protein variants from a single mRNA, which not only increases the diversity of proteins but also supports cellular differentiation. These mechanisms are not only biologically important, but also therapeutically relevant, as they can represent target structures for the development of new drugs.

This research was supported by Professor Hurt's ERC Advanced Grant, with additional funding from the National Key R&D Program of the People's Republic of China and other institutions. The results of this extensive collaboration were published in the journal “Cell Research”, which highlights the relevance of the findings in the scientific community.