2005
DOI: 10.1074/jbc.m505060200
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The Prp19-associated Complex Is Required for Specifying Interactions of U5 and U6 with Pre-mRNA during Spliceosome Activation

Abstract: Activation of the spliceosome involves a major structural change in the spliceosome, including release of U1 and U4 small nuclear ribonucleoprotein particles and the addition of a large protein complex, the Prp19-associated complex. We previously showed that the Prp19-associated complex is required for stable association of U5 and U6 with the spliceosome after U4 is released. Changes within the spliceosome upon binding of the Prp19-associated complex include remodeling of the U6/5 splice site interaction and d… Show more

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Cited by 112 publications
(118 citation statements)
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“…This finding is in a good agreement with previous observations that the NTC (the yeast counterpart of the hPrp19/CDC5L complex) stably binds to the spliceosome after U4 dissociation and is required for spliceosome activation (Chan et al 2003;Chan and Cheng 2005). Among the proteins most prominent first in the B act complex, was hPrp17, the human homolog of the nonessential, yeast second-step factor Prp17.…”
Section: Protein Dynamics During the B To B Act Complex Transitionsupporting
confidence: 82%
See 1 more Smart Citation
“…This finding is in a good agreement with previous observations that the NTC (the yeast counterpart of the hPrp19/CDC5L complex) stably binds to the spliceosome after U4 dissociation and is required for spliceosome activation (Chan et al 2003;Chan and Cheng 2005). Among the proteins most prominent first in the B act complex, was hPrp17, the human homolog of the nonessential, yeast second-step factor Prp17.…”
Section: Protein Dynamics During the B To B Act Complex Transitionsupporting
confidence: 82%
“…The Prp19 protein, in the form of a heteromeric protein complex (the nineteen complex or NTC in yeast and the Prp19/CDC5L complex in humans) plays an essential role in spliceosome activation (Chan et al 2003;Makarova et al 2004). The NTC complex acts subsequent to U4 dissociation, stabilizing the association of U5 and U6 with the activated spliceosome (Chan et al 2003) and specifying the proper interaction of U5 and U6 with the pre-mRNA substrate prior to step 1 (Chan and Cheng 2005).…”
Section: Introductionmentioning
confidence: 99%
“…4 C and D). These conclusions are consistent with the NTC providing essential structural support for the activated spliceosome (21) by stabilizing interactions between the U5 and U6 snRNAs and the pre-mRNA (22). Furthermore, the NTC component Cwc2 has recently been proposed to tether the 5′SS:U6 snRNA duplex to the spliceosome's catalytic center including the essential U2:U6 snRNA duplex (helix I) immediately adjacent to the U2:BS duplex.…”
Section: Discussionsupporting
confidence: 69%
“…One possibility is that the NTC complex in the intact ILS engages in various protein-protein and protein-RNA contacts with the snRNPs and the IL RNA and that these hold the spliceosome together. Such a scaffolding function of the NTC was indicated by previous experiments showing that stable integration of the snRNPs in the activated spliceosome requires the NTC complex (Chan et al 2003;Chan and Cheng 2005). After Prp43-mediated disassembly of the ILS, some of these contacts are retained, yielding a distribution of the NTC between the U2 and U5 snRNPs and IL RNA that may reflect its different binding affinities for these components.…”
Section: Discussionmentioning
confidence: 91%