Genome complexity: spliceosome architecture (Introduction)

by David Turell , Thursday, October 31, 2024, 23:42 (23 days ago) @ David Turell

The latest description:

https://phys.org/news/2024-10-human-spliceosome-decade-reveals-blueprint.html

"The spliceosome edits genetic messages transcribed from DNA, allowing cells to create different versions of a protein from a single gene. The vast majority of human genes—more than nine in 10—are edited by the spliceosome. Errors in the process are linked to a wide spectrum of diseases including most types of cancer, neurodegenerative conditions and genetic disorders.

"The sheer number of components involved and the intricacy of its function has meant the spliceosome has remained elusive and uncharted territory in human biology—until now.

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"Every cell in the human body relies on precise instructions from DNA to function correctly. These instructions are transcribed into RNA, which then undergoes a crucial editing process called splicing. During splicing, non-coding segments of RNA are removed, and the remaining coding sequences are stitched together to form a template or recipe for protein production.

"While humans have about 20,000 protein-coding genes, splicing allows the production of at least five times as many proteins, with some estimates suggesting humans can create more than 100,000 unique proteins.(my bold)

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"Their work revealed that different components of the spliceosome have unique regulatory functions. Crucially, they found that proteins within the spliceosome's core are not just idle support workers but instead have highly specialized jobs in determining how genetic messages are processed, and ultimately, influence the diversity of human proteins.

"For example, one component selects which RNA segment is removed. Another component ensures cuts are made at the right place in the RNA sequence, while another one behaves like a chaperon or security guard, keeping other components from acting too prematurely and ruining the template before it's finished.

"The authors of the study compare their discovery to a busy post-production set in film or television, where genetic messages transcribed from DNA are assembled like raw footage.

"'You have many dozens of editors going through the material and making rapid decisions on whether a scene makes the final cut. It's an astonishing level of molecular specialization at the scale of big Hollywood productions, but there's an unexpected twist. Any one of the contributors can step in, take charge, and dictate the direction. Rather than the production falling apart, this dynamic results in a different version of the movie. It's a surprising level of democratization we didn't foresee," says Dr. Malgorzata Rogalska, co-corresponding author of the study."

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"Apart from cancer, there are many other diseases caused by faulty RNA molecules produced by mistakes in splicing. With a detailed map of the spliceosome, which the authors of the study have made publicly-available, researchers can now help pinpoint exactly where the splicing errors are occurring in a patient's cells."

Comment: comparison with putting a film together is a good way to conceive of this. The original article is highly sophisticated study:

https://www.science.org/doi/10.1126/science.adn8105