Abstract
Macromolecular complexes composed of proteins or proteins and nucleic acids rather than individual macromolecules mediate many cellular activities. Maintenance of these activities is essential for cell viability and requires the coordinated production of the individual complex components as well as their faithful incorporation into functional entities. Failure of complex assembly may have fatal consequences and can cause severe diseases. While many macromolecular complexes can form spontaneously in vitro, they often require aid from assembly factors including assembly chaperones in the crowded cellular environment. The assembly of RNA protein complexes implicated in the maturation of pre-mRNAs (termed UsnRNPs) has proven to be a paradigm to understand the action of assembly factors and chaperones. UsnRNPs are assembled by factors united in protein arginine methyltransferase 5 (PRMT5)- and survival motor neuron (SMN)-complexes, which act sequentially in the UsnRNP production line. While the PRMT5-complex pre-arranges specific sets of proteins into stable intermediates, the SMN complex displaces assembly factors from these intermediates and unites them with UsnRNA to form the assembled RNP. Despite advanced mechanistic understanding of UsnRNP assembly, our knowledge of regulatory features of this essential and ubiquitous cellular function remains remarkably incomplete. One may argue that the process operates as a default biosynthesis pathway and does not require sophisticated regulatory cues. Simple theoretical considerations and a number of experimental data, however, indicate that regulation of UsnRNP assembly most likely happens at multiple levels. This review will not only summarize how individual components of this assembly line act mechanistically but also why, how, and when the UsnRNP workflow might be regulated by means of posttranslational modification in response to cellular signaling cues.
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Acknowledgements
We thank Dr. Clemens Grimm, Structural Biology group, Biozentrum, University of Würzburg, for the help with the interpretation of the structural and functional consequences of posttranslational modifications in the PRMT5 and the SMN complex.
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This review has been edited in accordance to good scientific practice. The literature in the field of SMN function and pathology is, however, overwhelming. We apologize to those colleagues whose work could not be cited here due to space constrains.
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Gruss, O.J., Meduri, R., Schilling, M. et al. UsnRNP biogenesis: mechanisms and regulation. Chromosoma 126, 577–593 (2017). https://doi.org/10.1007/s00412-017-0637-6
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DOI: https://doi.org/10.1007/s00412-017-0637-6