Scientists shed light on mechanisms responsible for maturation of the splicing machinery

Alternative splicing is an extraordinarily complex process that requires the coordinated action of multiple proteins, each specialized in very specific functions. These proteins are assembled and matured, forming a kind of consortium of proteins that perform these gene reading functions.

The assembly process is tightly controlled, and any failure can result in genetic diseases, including some types of cancer.

In this study, the researchers have explored some of the factors that enable the assembly and maturation of the spliceosome, a multi-megadalton complex responsible for cell splicing and alternative splicing, specifically in the proteins RUVBL1 and RUVBL2.

The study of the atomic structure of these proteins by means of Cryo- Electron microscopy (cryo-EM), among other techniques, has revealed their functioning: RUVBL1 and RUVBL2 operate as scaffolding that interacts and connects components of the splicing machinery with various factors necessary for maturation, which, in turn, control the activity of the RUVBL1-RUVBL2 complex.

These results help us to understand some of the mechanisms responsible for the maturation of the splicing machinery. Several types of cancer present failures in the splicing processes, which is an advantage for tumor cells since these failures improve their rate of survival.

If we understand in detail the assembly and maturation mechanism of the spliceosome and the factors that control it, we will also be able to understand essential processes for life and their role in diseases such as cancer." stated the researchers.

Source:
Journal reference:

Serna, M., et al. (2021) CryoEM of RUVBL1–RUVBL2–ZNHIT2, a complex that interacts with pre-mRNA-processing-splicing factor 8. Nucleic Acids Research. doi.org/10.1093/nar/gkab1267.

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