The function of the NineTeen Complex (NTC) in regulating spliceosome conformations and fidelity during pre-mRNA splicing

Hogg, Rebecca; McGrail, Joanne C.; O’Keefe, Raymond T.

doi:10.1042/bst0381110

Cited by 100 publications

(114 citation statements)

References 50 publications

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“…These included MODIFIER OF SNC1 4 (MOS4) that shows homology to human Breast Cancer-Amplified Sequence 2, the Arabidopsis CELL DIVISION CYCLE5 (CDC5) Myb-transcription factor, and the WD-40 repeat PLEIOTROPIC REGULATORY LOCUS1 (Palma et al, 2007). Notably, their counterparts in humans and yeast interact with one another and with Prp19 (for Precursor RNA Processing 19) in the core of the Nineteen Complex (so named for Prp19) that is essential for catalytic activation of the spliceosome (Hogg et al, 2010). A proteomics approach for proteins interacting with MOS4 subsequently identified two closely related proteins with sequence homology to Prp19, termed MAC3A (for MOS4-associated complex 3A) and MAC3B (Monaghan et al, 2009).…”

Section: Factors Involved In As Of R Genes and Plant Defensementioning

confidence: 99%

Alternative Splicing at the Intersection of Biological Timing, Development, and Stress Responses

2013

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High-throughput sequencing for transcript profiling in plants has revealed that alternative splicing (AS) affects a much higher proportion of the transcriptome than was previously assumed. AS is involved in most plant processes and is particularly prevalent in plants exposed to environmental stress. The identification of mutations in predicted splicing factors and spliceosomal proteins that affect cell fate, the circadian clock, plant defense, and tolerance/sensitivity to abiotic stress all point to a fundamental role of splicing/AS in plant growth, development, and responses to external cues. Splicing factors affect the AS of multiple downstream target genes, thereby transferring signals to alter gene expression via splicing factor/AS networks. The last two to three years have seen an ever-increasing number of examples of functional AS. At a time when the identification of AS in individual genes and at a global level is exploding, this review aims to bring together such examples to illustrate the extent and importance of AS, which are not always obvious from individual publications. It also aims to ensure that plant scientists are aware that AS is likely to occur in the genes that they study and that dynamic changes in AS and its consequences need to be considered routinely.

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Section: Factors Involved In As Of R Genes and Plant Defensementioning

confidence: 99%

Alternative Splicing at the Intersection of Biological Timing, Development, and Stress Responses

2013

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“…18 Formation of the next intermediate in spliceosome assembly, the A complex, requires ATP hydrolysis and results in the stable recruitment of additional factors to the pre-mRNA, most notably the U2 snRNP. Proteomic analysis has shown that the Prp19 complex (PRP19C), which plays an important role in spliceosome activation, 19 is also associated with the spliceosome in A complex. 16 Following A complex formation, the U4/U6 and U5 snRNPs become associated with the spliceosome as part of a preassembled unit known as the tri-snRNP, forming the B complex.…”

Section: Ctd Structure and Modificationmentioning

confidence: 99%

The RNA polymerase C-terminal domain

David

Manley

2011

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W ork over the last two decades has provided a wealth of data indicating that the RNA polymerase II transcriptional machinery can play an important role in facilitating the splicing of its transcripts. In particular, the C-terminal domain of the RNA polymerase II large subunit (CTD) is central in the coupling of transcription and splicing. While this has long been assumed to involve physical interactions between splicing factors and the CTD, few functional connections between the CTD and such factors have been established. We recently used a biochemical approach to identify a splicing factor that interacts directly with the CTD to activate splicing and, in doing so, may play a role in the process of spliceosome assembly.

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“…In this context, the recent demonstration of a direct interaction between Cwc24 and Cef1 is of interest (Goldfeder and Oliveira 2008). Cef1 is a core protein of the NTC complex, which acts as a major assembly platform, integrating and coordinating many molecular interactions in B act and B* complexes (Tsai et al 1999;Hogg et al 2010). An alternative primary target of Prp2 could be one of the U2 SF3a/b proteins, which are known to interact with the premRNA near the BS.…”

Section: Cwc24 Functions In the Generation Of An Active Spliceosome Bmentioning

confidence: 99%

Prp2-mediated protein rearrangements at the catalytic core of the spliceosome as revealed by dcFCCS

Ohrt¹,

Prior²,

Dannenberg³

et al. 2012

RNA

132

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The compositional and conformational changes during catalytic activation of the spliceosome promoted by the DEAH box ATPase Prp2 are only poorly understood. Here, we show by dual-color fluorescence cross-correlation spectroscopy (dcFCCS) that the binding affinity of several proteins is significantly changed during the Prp2-mediated transition of precatalytic B act spliceosomes to catalytically activated B* spliceosomes from Saccharomyces cerevisiae. During this step, several proteins, including the zinc-finger protein Cwc24, are quantitatively displaced from the B* complex. Consistent with this, we show that Cwc24 is required for step 1 but not for catalysis per se. The U2-associated SF3a and SF3b proteins Prp11 and Cus1 remain bound to the B* spliceosome under near-physiological conditions, but their binding is reduced at high salt. Conversely, high-affinity binding sites are created for Yju2 and Cwc25 during catalytic activation, consistent with their requirement for step 1 catalysis. Our results suggest high cooperativity of multiple Prp2-mediated structural rearrangements at the spliceosome's catalytic core. Moreover, dcFCCS represents a powerful tool ideally suited to study quantitatively spliceosomal protein dynamics in equilibrium.

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The function of the NineTeen Complex (NTC) in regulating spliceosome conformations and fidelity during pre-mRNA splicing

Cited by 100 publications

References 50 publications

Alternative Splicing at the Intersection of Biological Timing, Development, and Stress Responses

Alternative Splicing at the Intersection of Biological Timing, Development, and Stress Responses

The RNA polymerase C-terminal domain

Prp2-mediated protein rearrangements at the catalytic core of the spliceosome as revealed by dcFCCS

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