pre-mRNA processing factor 40: Biological Overview | References
Gene name - pre-mRNA processing factor 40
Synonyms - CG3542
Cytological map position - 23C4-23C4
Function - Splicing factor
Keywords - splice factor - regulates histone mRNA expression by modulating transcription - constituent of histone locus body, a chromatin-associated nuclear body that associates with replication-dependent histone gene clusters - regulates alternative splicing of Neurexin IV
Symbol - Prp40
FlyBase ID: FBgn0031492
Genetic map position - chr2L:3,023,226-3,026,439
Classification - FF: FF domain, WW: WW domain, PRP40: Splicing factor [RNA processing and modification]
Cellular location - nuclear
In eukaryotes, a large amount of histones must be synthesized during the S phase of the cell cycle to package newly synthesized DNA into chromatin. The transcription and 3' end processing of histone pre-mRNA are controlled by the histone locus body (HLB), which is assembled in the H3/H4 promoter. This study identified the Drosophila Prp40 pre-mRNA processing factor (dPrp40) as a novel HLB component. dPrp40 is essential for Drosophila development, with functionally conserved activity in vertebrates and invertebrates. It was observed that dPrp40 is fundamental in endocycling cells, highlighting a role for this factor in mediating replication efficiency in vivo. The depletion of dPrp40 from fly cells inhibited the transcription but not the 3' end processing of histone mRNA. These results establish that dPrp40 is an essential gene for Drosophila development that can localize to the HLB and may participate in histone mRNA biosynthesis (Prieto-Sanchez, 2019).
In eukaryotic cells, the nucleus is compartmentalized and contains several dynamic nonmembrane-bound structures referred to as nuclear bodies or nuclear compartments, which are essential for the correct maintenance of nuclear architecture and the gene-regulatory processes that occur within the nucleus. The study of the constituents and the spatial and dynamic properties of these nuclear bodies is essential for understanding the regulation of gene expression programs, which are critical for cell stability and survival. Given the importance of nuclear bodies in controlling how gene expression is exerted, alterations in the regulation or biosynthesis of these structures can lead to pathological consequences (Prieto-Sanchez, 2019).
Because of the absence of a delineated membrane, the structural integrity of nuclear bodies is mediated by protein-protein and/or protein-RNA interactions. This property and the rapid dynamics of nuclear bodies are consistent with a self-organization model in which the structure of a body is determined by the global interactions among its constituents. Although significant progress has been made regarding the role of these nuclear bodies in gene expression, understanding how they are assembled in the cell is still far from being understood. Many studies have led to two main distinct but not exclusive assembly models. While one model posits that assembly occurs through an ordered, hierarchical process through which constituents are assembled around a primordial scaffolding factor or RNA, the other model considers that self-organization is accomplished randomly without any particular ordered or hierarchical nuclear body assembly. More recently, a third model for nuclear body formation involves intracellular phase separation to promote the assembly of droplets of nuclear protein/RNA has been proposed (Zhu, 2015; Boeynaems, 2018; Marzluff, 2008). This model posits the existence of different nucleoplasmic phases with distinct physical properties through which proteins may transition to gain favorable thermodynamic states so that nuclear body assembly is mediated by this phase transition (Prieto-Sanchez, 2019).
Some nuclear bodies are also associated with specific gene loci, and this association with a specific nuclear function or activity may be important for their formation and function. The histone locus body (HLB) is a chromatin-associated nuclear body that specifically associates with replication-dependent histone gene clusters to coordinate the transcription and 3' end processing of histone pre-mRNA (Duronio, 2017; Marzluff, 2017; Marzluff, 2008). In Drosophila, the histone gene cluster is composed of ∼100 copies of tandemly arranged histone H1, H2a, H2b, H3 and H4 gene cassettes. Histones play a crucial role in the packaging of DNA into chromatin. Consistent with this role, histone expression is restricted to the early S phase of the cell cycle, which is tightly coupled to DNA synthesis (Marzluff, 2008). Defects in histone biosynthesis result in genomic instability, which may promote oncogenesis. Since the initial characterization of the HLB by the Gall laboratory (Liu, 2006), many factors have been identified as components of this nuclear body. Some of these factors are constitutively present in these nuclear bodies throughout the cell cycle, whereas others are recruited to the HLB only during the S phase when histone transcription is active. The first group of factors includes Multi sex combs (Mxc), FLASH, the U7 snRNP and Mute, whereas general and elongation transcription factors, such as RNA polymerase II (RNAPII), TBP, Spt6 and Myc, and factors regulating histone pre-mRNA processing, such as Symplekin and other proteins (Duronio, 2017), associate with the HLB upon the activation of histone gene transcription. The emerging picture is that the Drosophila HLB assembles through the hierarchical recruitment of components; Mxc and FLASH form the foundational HLB that is detected in the early embryo at cycle 10, and U7 snRNP and Mute are recruited at cycle 11 in the absence of histone mRNA transcription (White, 2011). A sequence located between the histone H3 and H4 genes contains the shared H3 and H4 promoter (hereafter, denoted as the H3/H4 promoter), which is essential for histone gene expression, and is required for the recruitment of Mxc and FLASH (Salzler, 2013). A significant number of proteins are subsequently joined to the HLB in a manner coupled to active histone gene transcription (Duronio, 2017). How the initial interaction of Mxc and FLASH with the histone loci occurs and what the actual composition of a fully formed HLB is remain to be resolved (Prieto-Sanchez, 2019).
Prp40 was initially identified as an essential yeast factor that participates as a scaffold in the early steps of spliceosome complex formation. Prp40 has a characteristic domain organization, with two WW domains in the N-terminus and five FF domains in the C-terminus, which is a structure shared by a relatively small number of proteins (Becerra, 2016). Strikingly, most of these structurally related proteins have been implicated in transcription and splicing regulation. There are two putative mammalian orthologs of Prp40, PRPF40A and PRPF40B. Based on phylogenomic data, PRPF40A appears to be more closely related to Prp40 than does PRPF40B, which emerged much later in evolutionary history probably due to a gene duplication event from an ancestral PRPF40A. PRPF40A and PRPF40B interact with the transcription and splicing machineries, and at least for PRPF40B, the modulation of alternative splice site selection in apoptosis-related genes has been shown (Becerra, 2016; Becerra, 2015). The Drosophila ortholog of Prp40, herein denoted dPrp40, encoded by the CG3542 gene, shares 23% and 41% sequence identity with the yeast Prp40 and the human PRPF40A proteins, which suggests that the function of these proteins in forming bridges between the 5' and 3' splice sites in the first spliceosomal complex might be conserved. In fact, the regulation of alternative pre-mRNA splicing of the glial-specific cell-adhesion molecule Neurexin IV by dPrp40 has been reported (Rodrigues, 2012; Prieto-Sanchez, 2019 and references therein).
This study characterize dPrp40 and identifies a putative new role for this protein in histone mRNA transcription. dPrp40 localizes to the Drosophila HLB during prophase after the incorporation of the HLB primary protein components. dPrp40 is essential for Drosophila development. Moreover, dPrp40 and its human orthologs can rescue the phenotype of dPrp40 mutant flies, demonstrating a functional conservation of eukaryotic Prp40 activities in vivo. An essential requirement is shown for for dPrp40 in endocycling cells, highlighting a role for this factor in the replication efficiency in vivo. In a molecular context, this study shows that the depletion of dPrp40 from fly cells inhibits histone mRNA transcription without affecting the 3' maturation of histone mRNA. Furthermore, H3/H4-dependent transcription, which is essential for HLB assembly and high-level histone gene expression (Salzler, 2013), is rescued by overexpressing dPrp40 in the depleted cells. Together, these results establish that dPrp40 is required for normal embryonic development and that dPrp40 can localize to the HLB and might regulate histone gene transcription, which could have important consequences for the cell cycle and maturation, development and viability (Prieto-Sanchez, 2019).
This study performed experiments to characterize the function of Prp40 (dPrp40) in Drosophila. dPrp40 was shown to be essential for Drosophila viability and development via siRNA-mediated depletion and single P element-mediated gene disruption approaches. Conditional knockdown of dPrp40 using different drivers resulted in abnormal phenotypes and increased apoptotic cells in certain regions of wing imaginal discs. These abnormal phenotypes were rescued by expression of the human orthologs of Prp40, indicating that the fly and human proteins have shared functions that affect cell viability. In agreement with this result, it was found previously that PRPF40B depletion increased both the number of Fas/CD95 receptors and cell apoptosis in mammalian cells, thus suggesting a role for this protein in programmed cell death (Becerra, 2015). The pleiotropic effects caused by the lack of dPrp40 expression, however, may indicate that dPrp40 also regulates other genes. In fact, transgenic PRPF40A expression resulted in a faint Notch-like phenotype with wing margin 'notches', which may suggest either an effect of the overexpressed protein on Notch function or an involvement of dPrp40 in the Notch signaling pathway. Recently a transcriptome analysis of dPrp40 fly mutants was performed, and the preliminary results support the involvement of dPrp40 in the Notch signaling pathway. Further study is required to determine the molecular targets and signaling pathways regulated by dPrp40 (Prieto-Sanchez, 2019).
This study also identified a putative function for dPrp40 in the regulation of histone gene transcription. The localization of dPrp40 to the HLB pointed to a possible role of dPrp40 in the regulation of histone gene expression. This hypothesis is supported by the observation that dPrp40 loss-of-function mutants exhibited altered S phase progression and decreased histone gene mRNA expression. The 3' end processing of pre-mRNAs plays an important role in the regulation of histone mRNAs, and HLB components are required for the 3' end maturation of histone mRNAs (Duronio, 2017 and references therein). The results showed that dPrp40 depletion in Drosophila cells does not result in the polyadenylation of histone mRNAs, indicating that dPrp40 is not required for the 3' end processing of histone pre-mRNAs in vivo. These experiments, however, suggest that dPrp40 regulates histone mRNA expression by modulating transcription. An effect of dPrp40 on transcription synthesis is favored based on data using histone promoters and ChIP analysis. A possible effect of dPrp40 on RNA stability remains to be studied. The regulation of histone gene expression at the level of transcription by dPrp40 was an unexpected finding. The only function described for Prp40 in Drosophila is the regulation of alternative pre-mRNA splicing of the glial-specific cell adhesion molecule Neurexin IV (Rodrigues, 2012). This role of dPrp40 in the splicing process agrees with the proposed role for yeast Prp40 in the early steps of spliceosome formation and with previous data in Drosophila supporting a role for the mammalian Prp40 ortholog PRPF40B in pre-mRNA splicing (Becerra, 2015). Other data challenge this view and suggest alternative mechanisms of action, including a role for this protein in the later steps of spliceosome assembly and in transcriptional regulation (reviewed in Becerra, 2016), which would be consistent with the unexpected data suggesting a role for dPrp40 in histone mRNA transcription. However, the possibility that dPrp40 is regulating other cellular processes and causing phenotypic defects by modulating the pre-mRNA alternative splicing of important Drosophila genes cannot be excluded. In fact, the FF domains that are critical for dPrp40 function are responsible for binding to Luc7 and Snu71, two proteins within the U1 snRNP complex. The effect of dPrp40 on splicing, however, seems not to be prominent in Drosophila tissues, according to the results of the current genome-wide analysis of transcript- and exon-level changes in siRNA flies. Further studies will be required to fully characterize the function of the dPrp40 protein in mRNA synthesis and processing (Prieto-Sanchez, 2019).
The data demonstrate that dPrp40 depletion results in growth defects and that dPrp40 localizes to the HLB and regulates histone gene transcription. Although it is tempting to link the phenotypic defects resulting from dPrp40 loss of function with histone gene expression, it is believed that dPrp40 may regulate cell growth and proliferation by mechanism(s) other than the regulation of histone genes. The current data support this notion. First, this study showed that dPrp40 associates with the HLB during interphase and early mitosis. Despite the colocalization of dPrp40 with MPM2, which is associated with the HLB only during S phase when the bulk of histone protein synthesis occurs, dPrp40 staining was also detected during the starting phase of cell division, when DNA replication is over. These data are consistent with dPrp40 being present in the HLB throughout interphase and early mitosis and therefore disengaged from the activation of histone gene transcription. The small increase in dPrp40 binding at the promoter sequences in cells in late S phase compared to at the G1/S transition is not in disagreement with this hypothesis. Second, whereas the expression of the ΔWWdPrp40 construct resulted in the deficient accumulation of dPrp40 in the HLB, indicating a less-important role of the FF domains in the localization of dPrp40 to this nuclear compartment, the FF domains of dPrp40 were essential for rescuing the phenotype resulting from the loss of dPrp40 and were also important in the activation of the histone H3/H4 promoter. Therefore, and in the absence of convincing evidence of dPrp40 having a direct role in histone mRNA metabolism, these observations suggest that the growth defects resulting from dPrp40 loss of function were not linked to the localization of dPrp40 at the HLB and the regulation of histone gene expression (Prieto-Sanchez, 2019).
An interesting question that arises from this study regards the means by which dPrp40 might be targeted to the HLB. Seminal work by Duronio provided evidence for an ordered process in Drosophila HLB assembly. Mxc and FLASH are first recruited to the HLB, whereas the other components, including U7 snRNP, Mute and other transcription and mRNA factors, are subsequently recruited in a histone gene transcription-dependent fashion (Duronio, 2017). Because of the reported association of the WW and FF domains of Prp40 with the phosphorylated C-terminal domain (phospho-CTD) of RNAPII (Morris, 2000), an exciting possibility is that dPrp40 might be recruited to the HLB via a mechanism involving the phospho-CTD. Importantly, phosphorylated RNAPII is highly associated with the HLB during the S phase, when histone mRNA transcription activation occurs. Several other interpretations are also possible. Interactions among HLB components are necessary for the ordered recruitment of additional HLB factors. For example, the C-terminal region of FLASH is necessary for the recruitment of U7 snRNP to the HLB. Similarly, dPRP40 might be recruited to the HLB complex through interactions of its WW domains with other components of the complex. Another mechanism potentially collaborating in the formation of the HLB complex involves phosphorylation by Cyclin E-Cdk2, which is essential for histone mRNA expression. Although Mxc is a target of this kinase, Mxc localization to the HLB does not require Cyclin E-Cdk2 activity (White, 2011). The Spt6 HLB component is specifically immunoprecipitated by the phosphoprotein epitope-specific MPM2 monoclonal antibody, and phosphate treatment of the extract disrupts the interaction of Spt6 with the HLB complex, thus suggesting a role of Cyclin E-Cdk2 activity in Spt6 localization to the HLB (White, 2011). Because of the cyclin-dependent kinase consensus motif at position 739 of dPrp40, assessing the localization of dPrp40 to the HLB with respect to Cyclin E-Cdk2 activity would be informative (Prieto-Sanchez, 2019).
In summary, this study has characterized the function of Prp40 in Drosophila and has identified dPrp40 as a new component of the HLB. dPrp40 was also shown to be required for normal embryonic development and might participate in histone mRNA biosynthesis. Further study of dPrp40 will clearly be useful to define the detailed mechanism of its function (Prieto-Sanchez, 2019).
The differentiation of the blood-brain barrier (BBB) is an essential process in the development of a complex nervous system and depends on alternative splicing. In the fly BBB, glial cells establish intensive septate junctions that require the cell-adhesion molecule Neurexin IV. Alternative splicing generates two different Neurexin IV isoforms: Neurexin IV(exon3), which is found in cells that form septate junctions, and Neurexin IV(exon4), which is found in neurons that form no septate junctions. This study shows that the formation of the BBB depends on the RNA-binding protein HOW (Held out wings), which triggers glial specific splicing of Neurexin IV(exon3). Using a set of splice reporters, this study shows that one HOW-binding site is needed to include one of the two mutually exclusive exons 3 and 4, whereas binding at the three further motifs is needed to exclude exon 4. The differential splicing is controlled by nuclear access of HOW and can be induced in neurons following expression of nuclear HOW. Using a novel in vivo two-color splicing detector, a screen was carried out for genes required for full HOW activity. This approach identified Cyclin-dependent kinase 12 (Cdk12) and the splicesosomal component Prp40 as major determinants in regulating HOW-dependent splicing of Neurexin IV. Thus, in addition to the control of nuclear localization of HOW, the phosphorylation of the C-terminal domain of the RNA polymerase II by Cdk12 provides an elegant mechanism in regulating timed splicing of newly synthesized mRNA molecules (Rodrigues, 2012).
The multi-component cytoplasmic dynein transports cellular cargoes with the help of another multi-component complex dynactin, but not know enough is known about factors that may affect the assembly and functions of these proteins. From a genetic screen for mutations affecting early-endosome distribution in Aspergillus nidulans, this study identified the prp40A(L438*) mutation in Prp40A, a homologue of Prp40, an essential RNA-splicing factor in the budding yeast. Prp40A is not essential for splicing, although it associates with the nuclear splicing machinery. The prp40A(L438*) mutant is much healthier than the prp40A mutant, but both mutants exhibit similar defects in dynein-mediated early-endosome transport and nuclear distribution. In the prp40A(L438*) mutant, the frequency but not the speed of dynein-mediated early-endosome transport is decreased, which correlates with a decrease in the microtubule plus-end accumulations of dynein and dynactin. Within the dynactin complex, the actin-related protein Arp1 forms a mini-filament. In a pull-down assay, the amount of Arp1 pulled down with its pointed-end protein Arp11 is lowered in the prp40A(L438*) mutant. In addition, it was found from published interactome data that a mammalian Prp40 homologue PRPF40A interacts with Arp1. Thus, Prp40 homologues may regulate the assembly or function of dynein-dynactin and their mechanisms deserve to be further studied (Qiu, 2020).
Because of their sessile nature, plants have adopted varied strategies for growing and reproducing in an ever-changing environment. Control of mRNA levels and pre-mRNA alternative splicing are key regulatory layers that contribute to adjust and synchronize plant growth and development with environmental changes. Transcription and alternative splicing are thought to be tightly linked and coordinated, at least in part, through a network of transcriptional and splicing regulatory factors that interact with the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II. One of the proteins that has been shown to play such a role in yeast and mammals is pre-mRNA-PROCESSING PROTEIN 40 (PRP40, also known as CA150, or TCERG1). In plants, members of the PRP40 family have been identified and shown to interact with the CTD of RNA Pol II, but their biological functions remain unknown. The role was studied of AtPRP40C in Arabidopsis thaliana growth, development and stress tolerance, as well as its impact on the global regulation of gene expression programs. Tprp40c knockout mutants displayed a late-flowering phenotype under long day conditions, associated with minor alterations in red light signaling. An RNA-seq based transcriptome analysis revealed differentially expressed genes related to biotic stress responses and also differentially expressed as well as differentially spliced genes associated with abiotic stress responses. Indeed, the characterization of stress responses in prp40c mutants revealed an increased sensitivity to salt stress and an enhanced tolerance to Pseudomonas syringae pv. maculicola (Psm) infections. This constitutes the most thorough analysis of the transcriptome of a prp40 mutant in any organism, as well as the first characterization of the molecular and physiological roles of a member of the PRP40 protein family in plants. These results suggest that PRP40C is an important factor linking the regulation of gene expression programs to the modulation of plant growth, development, and stress responses (Hernando, 2019).
Altered splicing contributes to the pathogenesis of human blood disorders including myelodysplastic syndromes (MDS) and leukemias. This study characterize the transcriptomic regulation of PRPF40B, which is a splicing factor mutated in a small fraction of MDS patients.A full PRPF40B knockout (KO) was generated in the K562 cell line by CRISPR/Cas9 technology and its levels were rescued by transient overexpression of wild-type (WT), P383L or P540S MDS alleles. Using RNA sequencing, hundreds of differentially expressed genes and alternative splicing (AS) events were identified in the KO that are rescued by WT PRPF40B, with a majority also rescued by MDS alleles, pointing to mild effects of these mutations. Among the PRPF40B-regulated AS events, a net increase was found in exon inclusion in the KO, suggesting that this splicing factor primarily acts as a repressor. PRPF40B-regulated splicing events are likely cotranscriptional, affecting exons with A-rich downstream intronic motifs and weak splice sites especially for 5' splice sites, consistent with its PRP40 yeast ortholog being part of the U1 small nuclear ribonucleoprotein. Loss of PRPF40B in K562 induces a KLF1 transcriptional signature, with genes involved in iron metabolism and mainly hypoxia, including related pathways like cholesterol biosynthesis and Akt/MAPK signaling. A cancer database analysis revealed that PRPF40B is lowly expressed in acute myeloid leukemia, whereas its paralog PRPF40A expression is high as opposed to solid tumors. Furthermore, these factors negatively or positively correlated with hypoxia regulator HIF1A, respectively. These data suggest a PRPF40B role in repressing hypoxia in myeloid cells and that its low expression might contribute to leukemogenesis (Lorenzini, 2019).
The first stable complex formed during the assembly of spliceosomes onto pre-mRNA substrates in mammals includes U1 snRNP, which recognizes the 5' splice site, and the splicing factors SF1 and U2AF, which bind the branch point sequence, polypyrimidine tract, and 3' splice site. The 5' and 3' splice site complexes are thought to be joined together by protein-protein interactions mediated by factors that ensure the fidelity of the initial splice site recognition. This study identified and characterized PRPF40B, a putative mammalian ortholog of the U1 snRNP-associated yeast splicing factor Prp40. PRPF40B is highly enriched in speckles with a behavior similar to splicing factors. PRPF40B interacts directly with SF1 and associates with U2AF(65). Accordingly, PRPF40B colocalizes with these splicing factors in the cell nucleus. Splicing assays with reporter minigenes revealed that PRPF40B modulates alternative splice site selection. In the case of Fas regulation of alternative splicing, weak 5' and 3' splice sites and exonic sequences are required for PRPF40B function. Placing these data in a functional context, it was also shown that PRPF40B depletion increased Fas/CD95 receptor number and cell apoptosis, which suggests the ability of PRPF40B to alter the alternative splicing of key apoptotic genes to regulate cell survival (Becerra, 2015).
Previous work showed that the WW domain of the prolyl isomerase, Ess1, can bind the phosphorylated carboxyl-terminal domain (phospho-CTD) of the largest subunit of RNA Polymerase II. Analysis of phospho-CTD binding by four other WW domain-containing Saccharomyces cerevisiae proteins indicates the splicing factor, Prp40, and the RNA polymerase II ubiquitin ligase, Rsp5, can also bind the phospho-CTD. The identification of Prp40 as a phospho-CTD binding protein represents the first demonstration of direct interaction between a documented splicing factor and the phospho-CTD. Domain dissection studies reveal that phospho-CTD binding occurs at multiple locations in Prp40, including sites in both the WW and FF domain regions. Because the conserved repeats of the CTD make it an ideal ligand for multi-site binding events, the implications of multi-site binding are discussed. These data suggest a mechanism by which the phospho-CTD of elongating RNA polymerase II facilitates commitment complex formation by juxtaposing the 5' and 3' splice sites (Morris, 2000).
Search PubMed for articles about Drosophila Prp40
Becerra, S., Montes, M., Hernandez-Munain, C. and Sune, C. (2015). Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF65 and modulates alternative pre-mRNA splicing in vivo. RNA 21(3): 438-457. PubMed ID: 25605964
Becerra, S., Andres-Leon, E., Prieto-Sanchez, S., Hernandez-Munain, C. and Sune, C. (2016). Prp40 and early events in splice site definition. Wiley Interdiscip Rev RNA 7(1): 17-32. PubMed ID: 26494226
Boeynaems, S., Alberti, S., Fawzi, N. L., Mittag, T., Polymenidou, M., Rousseau, F., Schymkowitz, J., Shorter, J., Wolozin, B., Van Den Bosch, L., Tompa, P. and Fuxreiter, M. (2018). Protein phase separation: a new phase in cell biology. Trends Cell Biol 28(6): 420-435. PubMed ID: 29602697
Duronio, R. J. and Marzluff, W. F. (2017). Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body. RNA Biol 14(6): 726-738. PubMed ID: 28059623
Hernando, C. E., Garcia Hourquet, M., de Leone, M. J., Careno, D., Iserte, J., Mora Garcia, S. and Yanovsky, M. J. (2019). A role for pre-mRNA-PROCESSING PROTEIN 40C in the control of growth, development, and stress tolerance in Arabidopsis thaliana. Front Plant Sci 10: 1019. PubMed ID: 31456814
Liu, J. L., Buszczak, M. and Gall, J. G. (2006). Nuclear bodies in the Drosophila germinal vesicle. Chromosome Res 14(4): 465-475. PubMed ID: 16821140
Lorenzini, P. A., Chew, R. S. E., Tan, C. W., Yong, J. Y., Zhang, F., Zheng, J. and Roca, X. (2019). Human PRPF40B regulates hundreds of alternative splicing targets and represses a hypoxia expression signature. RNA 25(8): 905-920. PubMed ID: 31088860
Marzluff, W. F., Wagner, E. J. and Duronio, R. J. (2008). Metabolism and regulation of canonical histone mRNAs: life without a poly(A) tail. Nat Rev Genet 9(11): 843-854. PubMed ID: 18927579
Morris, D. P. and Greenleaf, A. L. (2000). The splicing factor, Prp40, binds the phosphorylated carboxyl-terminal domain of RNA polymerase II. J Biol Chem 275(51): 39935-39943. PubMed ID: 10978320
Prieto-Sanchez, S., Moreno-Castro, C., Hernandez-Munain, C. and Sune, C. (2020). Drosophila Prp40 localizes to the histone locus body and regulates gene transcription and development. J Cell Sci. PubMed ID: 32094262
Qiu, R., Zhang, J. and Xiang, X. (2020). The splicing-factor Prp40 affects dynein-dynactin function in Aspergillus nidulans. Mol Biol Cell 31(12): 1289-1301. PubMed ID: 32267207
Rodrigues, F., Thuma, L. and Klambt, C. (2012). The regulation of glial-specific splicing of Neurexin IV requires HOW and Cdk12 activity. Development 139(10): 1765-1776. PubMed ID: 22461565
Salzler, H. R., Tatomer, D. C., Malek, P. Y., McDaniel, S. L., Orlando, A. N., Marzluff, W. F. and Duronio, R. J. (2013). A sequence in the Drosophila H3-H4 Promoter triggers histone locus body assembly and biosynthesis of replication-coupled histone mRNAs. Dev Cell 24(6): 623-634. PubMed ID: 23537633
White, A. E., Burch, B. D., Yang, X. C., Gasdaska, P. Y., Dominski, Z., Marzluff, W. F. and Duronio, R. J. (2011). Drosophila histone locus bodies form by hierarchical recruitment of components. J Cell Biol 193(4): 677-694. PubMed ID: 21576393
Zhu, L. and Brangwynne, C. P. (2015). Nuclear bodies: the emerging biophysics of nucleoplasmic phases. Curr Opin Cell Biol 34: 23-30. PubMed ID: 25942753
date revised: 22 June 2020
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