Generally, the expression of genes encoding proteins that are part of the same pathway is regulated in a coordinated manner, either at the level of transcription, or post-transcriptionally. One of the challenges of systems biology is to understand how the interplay of individual cellular components gives rise to cellular behaviors such as cell division, apoptosis and differentiation. P.A discussion of protocols and approaches to the preparation of high-quality cDNA libraries Current Opinion in Structural Biology, 36, 48-57.įica, Sebastian M., Small, E.C., Mefford, M., and Staley, J. CryoEM structures of two spliceosomal complexes: starter and dessert at the spliceosome feast. P., Fica, Sebastian M., Lin, P.-C., Newman, A. This review provided an overview of the initial spliceosome structures obtained by electron microscopy and placed their findings in the context of previous genetic and biochemical studies. Cryo-electron microscopy snapshots of the spliceosome: structural insights into a dynamic ribonucleoprotein machine. These factors are likely to modulate splice site choice and alternative splicing.įica, Sebastian M.#, & Nagai, K.# (2017). This review provides a comprehensive summary of key structures of the human spliceosomes and conceptualizes the roles of human-specific splicing factors discovered in recent structures. Current Opinion in Structural Biology, 65, 139-148.
Cryo-EM snapshots of the human spliceosome reveal structural adaptions for splicing regulation. Nature Structural & Molecular Biology, 20, 728-734.įica, Sebastian M.# (2020).
A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation. This study presented definitive functional evidence that the spliceosome active site is composed of RNA, while proteins stabilise and organise the RNA-based active site but do not play a direct catalytic role. * Fica, Sebastian M., *Tuttle, N., Novak, T., Li, N.-S., Lu, J., Koodathingal, P., Dai, Q., Staley, J. This study demonstrated that the active site of the spliceosome forms an RNA triple helix, which is essential for proper positioning of the two active site catalytic metals. Evidence for a group II intron-like catalytic triplex in the spliceosome. This work presented one of the first two structures of a yeast catalytic spliceosome and revealed the structure of the active site and the role of branching factors. Cryo-EM structure of the spliceosome immediately after branching. E., Fica, Sebastian M., Oubridge, C., Newman, A. This work elucidated the spliceosome conformation competent to perform the second catalytic step of splicing for mRNA synthesis. Structure of a spliceosome remodelled for exon ligation. This structure of a yeast post-catalytic spliceosome revealed the mechanism for 3'-splice site docking at the active site.įica, Sebastian M.#, Oubridge, C., Galej, W. (2017) Postcatalytic spliceosome structure reveals mechanism of 3'-splice site selection. This factor is a tumor suppressor, which potentially implicates regulation of splicing catalysis in cancer pathology. We discovered a metazoan-specific splicing factor important for mRNA synthesis. The structure of a human post-catalytic spliceosome showed how mammalian spliceosomes co-opted additional protein factors to stabilize 3'-splice site docking. J., Nagai, K.# (2019) A human postcatalytic spliceosome structure reveals essential roles of metazoan factors for exon ligation. Here the Nagai and Ule labs developed Purified Spliceosome iCLIP (psiCLIP) to probe protein-RNA interactions in defined spliceosome complexes and reveal how the helicases Prp16 and Prp22 promote correct mRNA synthesis through dynamic binding on their RNA substrates.įeatured in an MRC LMB Insight on Research.įica, Sebastian M.#, Oubridge, C., Wilkinson, M. #corresponding authors.ĪTP-dependent helicases remodel the spliceosome and proofread splice site recognition. PsiCLIP reveals dynamic RNA binding by DEAH-box helicases before and after exon ligation. M., Fica, Sebastian M.#, Oubridge, C., Luscombe, N.M.#, Ule, J.#, Nagai, K.
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