Crooked neck is a component of the human spliceosome and implicated in the splicing process

Chung, Seyung; Zhou, Zhaolan; Huddleston, Kathleen A.; Harrison, Douglas A.; Reed, Robin; Coleman, Timothy A.; Rymond, Brian C.

doi:10.1016/s0167-4781(02)00368-8

Cited by 30 publications

(22 citation statements)

References 43 publications

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“…Interestingly, a U2AF-PRP19C connection appears to be conserved in yeast, as the yeast U2AF65 homolog Mud2 was shown to interact physically with a subunit of yeast PRP19C, Clf1 (Chung et al 1999). Clf1 has a human homolog, Crn, which has been shown to associate with spliceosomes (Chung et al 2002) but has not been found to associate with human PRP19C. Additional work will be necessary to identify the factor that bridges U2AF65 and PRP19C in mammalian cells.…”

Section: Discussionmentioning

confidence: 99%

The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65–Prp19 complex

David¹,

Boyne²,

Millhouse³

et al. 2011

Genes Dev.

165

159

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Pre-mRNA splicing is frequently coupled to transcription by RNA polymerase II (RNAPII). This coupling requires the C-terminal domain of the RNAPII largest subunit (CTD), although the underlying mechanism is poorly understood. Using a biochemical complementation assay, we previously identified an activity that stimulates CTD-dependent splicing in vitro. We purified this activity and found that it consists of a complex of two wellknown splicing factors: U2AF65 and the Prp19 complex (PRP19C). We provide evidence that both U2AF65 and PRP19C are required for CTD-dependent splicing activation, that U2AF65 and PRP19C interact both in vitro and in vivo, and that this interaction is required for activation of splicing. Providing the link to the CTD, we show that U2AF65 binds directly to the phosphorylated CTD, and that this interaction results in increased recruitment of U2AF65 and PRP19C to the pre-mRNA. Our results not only provide a mechanism by which the CTD enhances splicing, but also describe unexpected interactions important for splicing and its coupling to transcription.

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Section: Discussionmentioning

confidence: 99%

The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65–Prp19 complex

David¹,

Boyne²,

Millhouse³

et al. 2011

Genes Dev.

165

159

View full text Add to dashboard Cite

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“…10 The spliceosome components uncovered in our screen included: SNRPB (SmB/B'), one of 7 core structural spliceosome proteins that directly assemble on the U-rich snRNAs; 34 P14 (SF3B14), a protein that directly contacts the adenosine at the branch point and carries out the first transesterification reaction during splicing; 35 as well as the spliceosome associated components CWC22 36 and CRNKL1. 37 To understand how depletion of these spliceosome components increased cell survival in taxol, we transfected HeLa cells with a pool of 4 siRNAs designed against each of the indicated spliceosome components. At 24 h after transfection, taxol was added at a final concentration of 220 nM.…”

Section: Depletion Of Spliceosome Components Induces Cell Cycle Delaysmentioning

confidence: 99%

Graded requirement for the spliceosome in cell cycle progression

Karamysheva¹,

Díaz-Martínez

Warrington

et al. 2015

Cell Cycle

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Genome stability is ensured by multiple surveillance mechanisms that monitor the duplication, segregation, and integrity of the genome throughout the cell cycle. Depletion of components of the spliceosome, a macromolecular machine essential for mRNA maturation and gene expression, has been associated with increased DNA damage and cell cycle defects. However, the specific role for the spliceosome in these processes has remained elusive, as different cell cycle defects have been reported depending on the specific spliceosome subunit depleted. Through a detailed cell cycle analysis after spliceosome depletion, we demonstrate that the spliceosome is required for progression through multiple phases of the cell cycle. Strikingly, the specific cell cycle phenotype observed after spliceosome depletion correlates with the extent of depletion. Partial depletion of a core spliceosome component results in defects at later stages of the cell cycle (G2 and mitosis), whereas a more complete depletion of the same component elicits an early cell cycle arrest in G1. We propose a quantitative model in which different functional dosages of the spliceosome are required for different cell cycle transitions.

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“…The UtpA subcomplex is the first to assemble onto the pre-rRNA as it has been found to be associated with the rDNA and is required for its transcription (19). The UtpB subcomplex contains six proteins, each characterized by protein-protein interaction domains (Table 1): Utp1 (Pwp2), Utp12 (Dip2), Utp13, Utp18, and Utp21 contain WD40 repeats; Utp6 uniquely contains a half-a-TPR ([HAT] where TPR is tetratricopeptide repeat) domain (42), also referred to as a cl-TPR (crooked neck-like TPR) (9), crnTPR (crn-like TPR) (53), or RTPR (RNA-TPR) (4). Each of these proteins and their domains are conserved through eukaryotes, suggesting that the insight we gain by studying the assembly and function of this subcomplex in yeast is likely to extend to humans.…”

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confidence: 99%

A Direct Interaction between the Utp6 Half-a-Tetratricopeptide Repeat Domain and a Specific Peptide in Utp21 Is Essential for Efficient Pre-rRNA Processing

Champion

Lane

Jackrel³

et al. 2008

Molecular and Cellular Biology

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The small subunit (SSU) processome is a ribosome biogenesis intermediate that assembles from its subcomplexes onto the pre-18S rRNA with yet unknown order and structure. Here, we investigate the architecture of the UtpB subcomplex of the SSU processome, focusing on the interaction between the half-a-tetratricopeptide repeat (HAT) domain of Utp6 and a specific peptide in Utp21. We present a comprehensive map of the interactions within the UtpB subcomplex and further show that the N-terminal domain of Utp6 interacts with Utp18 while the HAT domain interacts with Utp21. Using a panel of point and deletion mutants of Utp6, we show that an intact HAT domain is essential for efficient pre-rRNA processing and cell growth. Further investigation of the Utp6-Utp21 interaction using both genetic and biophysical methods shows that the HAT domain binds a specific peptide ligand in Utp21, the first example of a HAT domain peptide ligand, with a dissociation constant of 10 M.In eukaryotes, ribosome biogenesis requires the coordinated processing and assembly of four ribosomal RNAs (rRNAs) and about 78 ribosomal proteins (49). In Saccharomyces cerevisiae, the 35S pre-rRNA is transcribed by RNA polymerase I in the nucleolus and is cleaved in several places to produce the mature 18S, 5.8S, and 25S rRNAs (Fig. 1). This process utilizes over 180 trans-acting factors and yet occurs fast enough to allow 2,000 ribosomes to be made each minute (for reviews, see references 16, 17, 22, 24, and 51). In this highly coordinated process, many factors assemble onto the nascent pre-rRNA as it is transcribed, forming large ribonucleoproteins (RNPs) that mature the small subunit (SSU) or large subunit (LSU) of the ribosome. Despite the identification of such trans-acting factors, the details of ribosome biogenesis remain elusive, as the complexity of ribosome biogenesis lies in the folding of prerRNAs and ribosomal proteins into functional ribosomes. Indeed, the frontier of ribosome synthesis investigation is to delineate the role(s) of each trans-acting factor in the production of the rRNA as it is modified, processed, and folded to become the mature ribosome (22).Ribosome biogenesis is a dynamic process in which transacting factors associate with and dissociate from the evolving pre-rRNA throughout its maturation. The initial assembly of factors involved in both SSU and LSU biogenesis with the 35S pre-rRNA has been termed the 90S preribosome, which is separated by cleavage in ITS1 into the SSU processome (required for SSU maturation) and the 66S preribosome (required for LSU maturation) (22). An RNP forming around the pre-18S rRNA has long been visualized in Miller chromatin spreads as a packed structure (35)

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Crooked neck is a component of the human spliceosome and implicated in the splicing process

Cited by 30 publications

References 43 publications

The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65–Prp19 complex

The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65–Prp19 complex

Graded requirement for the spliceosome in cell cycle progression

A Direct Interaction between the Utp6 Half-a-Tetratricopeptide Repeat Domain and a Specific Peptide in Utp21 Is Essential for Efficient Pre-rRNA Processing

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