Identified Proteins Working two Jobs

Two proteins involved in mRNA splicing have a second job. During cell division, when splicing is interrupted, they directly mediate chromosome segregation to the daughter cells. The study, which could identify new anti-tumor targets, has been conducted by researchers at Sapienza University and at the Institute of Molecular Biology and Pathology of the CNR in Rome. The results have been published in the journal eLife

Cell division (mitosis) is a complex process that generates two daughter cells starting from a parent cell. Before cell division, DNA, the genetic material containing all information necessary for the functions of the cell, is duplicated and packaged into the chromosomes, so that it can be equally distributed between the two daughter cells. The correct execution of mitosis is fundamental for many vital processes, and the alterations of this process contribute to carcinogenesis.

Researchers at the Department of Biology and Biotechnology “Charles Darwin” of Sapienza and at the Institute of Molecular Biology and Pathology of the National Research Council (CNR-IBPM), coordinated by Maurizio Gatti and Maria Patrizia Somma, discovered that Sf3A2 and Prp31, two proteins that play an essential role in splicing (the process of maturation of messenger RNAs, the molecules that copy the information contained in the DNA to translate it into the amino acid sequence of proteins), during mitosis perform a second function independent of splicing. The study has been published in the journal eLife.

"During mitosis," explains Maria Patrizia Somma, "the cell assembles a complex structure called spindle, which mainly consists of thin fibers formed by microtubules. The microtubules bind the chromosomes and mediate their correct positioning and their equal distribution between the two daughter cells. During mitosis, many vital processes aimed at protein synthesis such as mRNA splicing, the "cut and sew" of messenger RNAs, are interrupted. We wondered whether the proteins involved in the splicing process remain inactive during mitosis or perform splicing-independent functions. We found that Sf3A2 and Prp31 directly contribute to the correct binding of the chromosomes to the spindle microtubules. In the absence of these two proteins, the movement of the chromosomes is impaired due to the dispersion of the Ndc80/HEC1 protein, which is the main factor responsible for the interaction between the spindle microtubules and the chromosomes, and which is present in high concentrations in many tumors. The most relevant aspect of our results,"continues the researcher CNR-IBPM, "is that these proteins work directly both in the splicing process and mitosis, and can therefore be classified as “moonlighting” proteins, namely proteins that in addition to their main function, for which they have been initially characterized, perform a second job in another process or cellular structure."

"Our work," concludes Somma, "has an important cognitive value, because it opens the way to the study of other proteins involved in the splicing process to determine whether they have direct mitotic functions. Moreover, it expands the repertoire of mitotic proteins potentially relevant in tumorigenesis, which could constitute new anti-tumor targets." The work was conducted in collaboration with the University of Exeter (UK).


Splicing factors Sf3A2 and Prp31 have direct roles in mitotic chromosome segregation - Pellacani, C., Bucciarelli, E., Renda, F., Hayward, D., Palena, A., Chen, J., Bonaccorsi, S., Wakefield, J. G., & Somma, M. P. (2018) - eLife, 7, e40325. 


Further Information

Maurizio Gatti
Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome

Maria Patrizia Somma
Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome


Thursday, 21 February 2019

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