Concentrating pre-mRNA processing factors in the histone locus body facilitates efficient histone mRNA biogenesis

Tatomer, Deirdre C.; Terzo, Esteban A.; Curry, Kaitlin P.; Salzler, Harmony R.; Sabath, Ivan; Zapotoczny, Grzegorz; McKay, Daniel J.; Domiński, Zbigniew; Marzluff, William F.; Duronio, Robert J.

doi:10.1083/jcb.201504043

Cited by 79 publications

(124 citation statements)

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“…70 Similarly, a direct interaction between the NH 2 terminus of Lsm11 (in the U7 snRNP) and the NH 2 terminus of FLASH is necessary for pre-mRNA processing, but not for either U7 snRNP or FLASH to concentrate in the HLB. 72,73 In addition, the sequence in histone pre-mRNA that binds U7 snRNP is not required for U7 snRNP recruitment to the Drosophila HLB. 74 Instead, we found that the C terminus of FLASH, likely together with Mxc, is necessary for recruitment of U7 snRNP to the HLB.…”

Section: Self-organization Of the Hlbmentioning

confidence: 99%

“…74 Instead, we found that the C terminus of FLASH, likely together with Mxc, is necessary for recruitment of U7 snRNP to the HLB. 72 Thus, there are interactions among HLB components involved in assembling the HLB that are distinct from the interactions required for histone mRNA biosynthesis. Such modularity could explain how a protein like FLASH participates directly and separately in HLB formation and pre-mRNA processing.…”

Section: Self-organization Of the Hlbmentioning

confidence: 99%

“…Unlike other metazoan genes, where transcription can continue well 3 0 of the polyadenylation site, transcription termination is tightly coupled to histone mRNA processing in both Drosophila and mammals. 72,102,103 Drosophila RD histone pre-mRNA processing is normally very efficient, meaning that in wild type cells and animals only stem-loop RD histone mRNAs can be detected. RNA pol II pauses just 3 0 of the HDE, 104 and likely terminates immediately after processing since there are no detectable transcripts downstream of the HDE.…”

Section: Hlb Functionmentioning

confidence: 99%

“…RNA pol II pauses just 3 0 of the HDE, 104 and likely terminates immediately after processing since there are no detectable transcripts downstream of the HDE. 72 Failure to process histone mRNA in Drosophila results in continued transcription past the HDE and polyadenylation at cryptic polyadenylation sites 3 0 of the HDE in each histone gene. 105 Sufficient polyadenylated histone mRNA is produced in the absence of processing factors (e.g., U7 snRNP) to allow much of development to occur in Drosophila.…”

Section: Hlb Functionmentioning

confidence: 99%

“…Taking advantage of our knowledge of the molecular interactions of HLB components, 44,70,72,73,[99][100][101] we have performed genetic studies in Drosophila using mutant proteins that are either processing defective or unable to localize to the HLB. Unlike other metazoan genes, where transcription can continue well 3 0 of the polyadenylation site, transcription termination is tightly coupled to histone mRNA processing in both Drosophila and mammals.…”

Section: Hlb Functionmentioning

confidence: 99%

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Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

2017

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Metazoan replication-dependent (RD) histone genes encode the only known cellular mRNAs that are not polyadenylated. These mRNAs end instead in a conserved stem-loop, which is formed by an endonucleolytic cleavage of the pre-mRNA. The genes for all 5 histone proteins are clustered in all metazoans and coordinately regulated with high levels of expression during S phase. Production of histone mRNAs occurs in a nuclear body called the Histone Locus Body (HLB), a subdomain of the nucleus defined by a concentration of factors necessary for histone gene transcription and premRNA processing. These factors include the scaffolding protein NPAT, essential for histone gene transcription, and FLASH and U7 snRNP, both essential for histone pre-mRNA processing. Histone gene expression is activated by Cyclin E/Cdk2-mediated phosphorylation of NPAT at the G1-S transition. The concentration of factors within the HLB couples transcription with pre-mRNA processing, enhancing the efficiency of histone mRNA biosynthesis. KEYWORDSCell cycle; Drosophila; histone genes; mRNA processing; nuclear bodyProper utilization of genetic information in eukaryotes requires extensive three-dimensional organization of the genome and its associated proteins within the nucleus. The basic unit of genome organization is the nucleosome, an octamer of two molecules of each of the four core histone proteins (H2A, H2B, H3 and H4) that packages »147 base pairs of DNA. In mammalian cells, approximately 4£10 8 molcules of each core histone must be synthesized during S phase of the cell cycle to package the newly replicated DNA. Defects in this process result in genome instability that can contribute to human pathologies like cancer. Histone protein synthesis results from a large increase in production at the beginning of S phase of equal amounts of mRNAs encoding the four core nucleosomal histones, as well as histone H1. This highly coordinated gene expression event is performed by a set of transcription and pre-mRNA processing factors unique to replication dependent (RD) histone mRNA biosynthesis that assemble into a nuclear body tightly associated with RD histone genes called the histone locus body (HLB). HLB formation involves a combination of ordered and stochastic assembly steps, and cell cycle regulated changes in the HLB occur to activate histone gene expression during S phase. Here we describe the history of how the HLB was discovered followed by a discussion of HLB assembly mechanism and how the HLB functions in RD histone mRNA biosynthesis.

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Section: Self-organization Of the Hlbmentioning

confidence: 99%

Section: Self-organization Of the Hlbmentioning

confidence: 99%

Section: Hlb Functionmentioning

confidence: 99%

Section: Hlb Functionmentioning

confidence: 99%

Section: Hlb Functionmentioning

confidence: 99%

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Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

2017

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Cajal body function in genome organization and transcriptome diversity

et al. 2016

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Nuclear bodies contribute to nonrandom organization of the human genome and nuclear function. Using a major prototypical nuclear body, the Cajal body, as an example, we suggest that these structures assemble at specific gene loci located across the genome as a result of high transcriptional activity. Subsequently, target genes are physically clustered in close proximity in Cajal body-containing cells. However, Cajal bodies are observed in only a limited number of human cell types, including neuronal and cancer cells. Ultimately, Cajal body depletion perturbs splicing kinetics by reducing target small nuclear RNA (snRNA) transcription and limiting the levels of spliceosomal snRNPs, including their modification and turnover following each round of RNA splicing. As such, Cajal bodies are capable of shaping the chromatin interaction landscape and the transcriptome by influencing spliceosome kinetics. Future studies should concentrate on characterizing the direct influence of Cajal bodies upon small nuclear RNA gene transcriptional dynamics.

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Rapid regulations of metabolic reactions in Escherichia coli via light‐responsive enzyme redistribution

Huang

Sun

et al. 2022

Biotechnology Journal

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Protein-based condensates have been proposed to accelerate biochemical reactions by enriching reactants and enzymes simultaneously. Here, we engineered those condensates into a photo-activated switch in Escherichia coli (PhASE) to regulate enzymatic reactions via tuning the spatial correlation of enzymes and substrates. In this system, scaffold proteins undergo liquid-liquid phase separation (LLPS) to form light-responsive compartments. Tethered with a light-responsive protein, enzymes of interest (EOIs) can be recruited by those compartments from cytosol within only a few seconds after a pulse of light induction and fully released in 15 min. Furthermore, we managed to enrich small molecular substrates simultaneously with enzymes in the compartments and achieved the acceleration of luciferin and catechol oxidation by 2.3and 1.6-folds, respectively. We also developed a quantitative model to guide the further optimization of this demixed regulatory system. Our tool can thus be used to study the rapid redistribution of proteins, and reversibly regulate enzymatic reactions in E. coli.

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Concentrating pre-mRNA processing factors in the histone locus body facilitates efficient histone mRNA biogenesis

Cited by 79 publications

References 65 publications

Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body

Cajal body function in genome organization and transcriptome diversity

Rapid regulations of metabolic reactions in Escherichia coli via light‐responsive enzyme redistribution

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