2024-10-31 19:19:00
A team of Center for Genomic Regulation (CRG) of Barcelona describes in detail the first map of the human expliceosomethe most complex and intricate molecular machine inside every cell. It took more than ten years to complete this scientific feat, published in the journal ‘Science‘.
Its alteration is linked to processes such as cancer, neurodegenerative processes or various rare diseases. According to the researchers, “by knowing exactly what each part does, we can find completely new perspectives for addressing a broad spectrum of diseases.”
The spliceosome, one of the most complex molecular machines in human biology, modifies genetic messages transcribed from DNA, allowing cells to make multiple versions of proteins from a single gene. This process affects more than 90% of human genes and is linked to serious diseases such as cancer, neurodegenerative disorders and genetic conditions. Until now, the complexity and number of elements of the spliceosome have made it an enigma in biology.
CRG researchers have found that individual components of the spliceosome are highly specialized, which could unlock effective treatments with fewer side effects. “We now understand that the spliceosome is a set of finely tuned tools, not just a cut and paste machine,” says research leader Juan Valcárcel, revealing that some specific components could be transformed into new targets for drug therapy.
The spliceosome, the most complex molecular machine in human biology, coordinates the splicing process, which is crucial for RNA editing. This process eliminates noncoding segments, generating protein templates; Therefore, with approximately 20,000 genes, the human body can produce more than 100,000 unique proteins. This set of 150 proteins and five small RNAs was found to contain components with specialized roles and specific regulatory functions.
The CRG team demonstrated that each part contributes precisely to gene editing, revealing a functional complexity that allows for unprecedented protein diversity, a discovery that the researcher Malgorzata Rogalska described as “an astonishing level of molecular specialization”.
The study revealed that manipulation of the spliceosome component SF3B1, mutated in several types of cancer, such as melanoma and leukemia, causes a chain reaction in the cellular splicing network, pushing it beyond its adaptive capacity and towards self-destruction.
For cancer
This finding suggests that attacking this interconnected network could be a “Achilles heel«in tumor cells, where the spliceosome is highly vulnerable. This advancement offers new therapeutic opportunities by targeting defective RNA in splicing-related diseases, as indicated by Dom Reynolds, from Remix therapya company collaborating on the study.
In addition to its potential in oncology, this study offers hope for other disorders caused by errors in RNA splicing.
Valcárcel explains that the detailed map of the spliceosome, available to the public, facilitates the identification of specific errors in patient cellspromoting the development of personalized treatments for various diseases
#Spanish #team #designs #map #complex #molecular #machinery #cell
Interview: Mapping the Human Spliceosome with Juan Valcárcel
Time.news Editor: Good evening, everyone! Today, we have the pleasure of speaking with Dr. Juan Valcárcel from the Center for Genomic Regulation in Barcelona. Dr. Valcárcel recently led a groundbreaking study that unveiled the first detailed map of the human spliceosome, a monumental achievement in molecular biology. Thank you for joining us, Dr. Valcárcel!
Juan Valcárcel: Thank you for having me! It’s a pleasure to be here.
Time.news Editor: Let’s start with the basics. Could you explain what the spliceosome is and why it’s so significant in human biology?
Juan Valcárcel: Absolutely! The spliceosome is one of the most complex molecular machines in our cells. Its primary function is to modify the genetic messages that are transcribed from DNA into RNA. Specifically, it allows for splicing, which edits the RNA by removing noncoding segments and joining the coding portions together. This process is crucial because it enables a single gene to generate multiple proteins, a phenomenon known as alternative splicing. In fact, more than 90% of human genes undergo this process, which ultimately leads to the production of over 100,000 unique proteins.
Time.news Editor: Fascinating! In light of this complexity, can you share why mapping the spliceosome has taken such a long time?
Juan Valcárcel: It has indeed been a long journey. The intricacy of the spliceosome is truly staggering, involving around 150 proteins and five small RNAs. The challenge lies in understanding not only the number of components involved but also their specific roles and how they interact with each other. Our study, which spanned more than a decade, involved painstakingly piecing together the functions of these components to develop a comprehensive map.
Time.news Editor: That sounds incredibly detailed! What have you discovered about the roles of individual components within the spliceosome?
Juan Valcárcel: We’ve found that the individual components of the spliceosome are highly specialized. This means they do more than just cut and paste RNA; they have specific regulatory functions that are finely tuned to ensure precise gene editing. Understanding these roles opens up exciting avenues for potential drug therapies, especially since errors in splicing are linked to various diseases, including cancer and neurodegenerative disorders.
Time.news Editor: That’s an important point. Given the connection between spliceosome dysfunction and diseases, how do your findings impact the future of medical treatments?
Juan Valcárcel: Our research suggests that by targeting specific components of the spliceosome, we could develop more effective treatments with fewer side effects. For instance, instead of targeting broader pathways that may affect multiple systems, we can focus on these specialized roles to design drugs that more precisely address the underlying causes of diseases caused by splicing errors.
Time.news Editor: It sounds like this could revolutionize how we understand and treat certain conditions. What are some challenges you foresee as the findings are translated into practical treatments?
Juan Valcárcel: One significant challenge is ensuring that any proposed therapies are safe and effective in humans. Clinical trials will be crucial for understanding how targeted treatments interact with the complex systems of our bodies. Moreover, as we delve deeper into the mechanistic details of the spliceosome, we must remain cautious about unintended effects, given the essential roles of splicing in normal cellular function.
Time.news Editor: Indeed, safety is paramount in medical advancements. Before we conclude, what future directions do you envision for your research team following this monumental achievement?
Juan Valcárcel: Moving forward, we aim to explore the specific functions of each spliceosome component in greater depth. We hope to investigate how these components interact with other cellular machinery and pathways. Additionally, we’ll be examining how variations in spliceosome function contribute to different diseases, potentially uncovering new biomarkers for diagnosis or even novel therapeutic targets.
Time.news Editor: Thank you for sharing such insightful perspectives, Dr. Valcárcel! Your work is a testament to the incredible advancements in understanding human biology and its implications for medicine.
Juan Valcárcel: Thank you! I’m excited for what’s to come and am grateful for the opportunity to share our findings.
Time.news Editor: You’ve heard it here first! The mapping of the human spliceosome could open new doors in molecular biology and medicine. Stay tuned for more updates as this research evolves! Thank you for joining us today.