<i>Drosophila</i>stem loop binding protein coordinates accumulation of mature histone mRNA with cell cycle progression

Sullivan, Eileen Brainne; Santiago, Carlos; Parker, Emily D.; Domiński, Zbigniew; Yang, Xiaocui; Lanzotti, David J.; Ingledue, Tom C.; Marzluff, William F.; Duronio, Robert J.

doi:10.1101/gad.862801

Cited by 129 publications

(217 citation statements)

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“…118 In Drosophila the maximal requirement for histone mRNA synthesis is likely to be during oogenesis when large amounts of maternal histone mRNA and protein are deposited into the egg. Several mutations that affect the HLB and histone pre-mRNA processing result in female sterility, 32,72,105,107 suggesting that the HLB may be particularly important during oogenesis, either in proper development of the egg 107 or in production of sufficient maternal histone mRNA for the embryo. 105,108 Interestingly, one well-studied organism, C. elegans, apparently lacks an HLB, although their histone mRNAs end in a stem loop and associate with SLBP.…”

Section: Discussionmentioning

confidence: 99%

“…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. 106,107 We can detect both poly AC histone RNA and nascent read-through unprocessed RNAs by nuclease protection and in situ hybridization assays, allowing us to quantitatively determine the efficiency of histone pre-mRNA processing in various tissues.…”

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: Discussionmentioning

confidence: 99%

Section: Hlb Functionmentioning

confidence: 99%

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

2017

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“…Thus, SLBP functions as a versatile regulator that ensures high levels of histone mRNAs and proteins only during S phase concomitant with DNA replication and prevents harmful accumulation of free histone proteins in the cell outside S phase. Not surprisingly, a deficit of SLBP results in defects in chromosome condensation due to the lack of histones and impair early developmental stages in Drosophila (Sullivan et al, 2001) and C. elegans (Kodama et al, 2002;Pettitt et al, 2002). …”

Section: Stem-loop Binding Protein (Slbp)mentioning

confidence: 99%

“…Drosophila SLBP contains a readily recognizable RNA binding domain (RBD) but otherwise has no similarity to SLBP from vertebrate species (Sullivan et al, 2001). The RBD in Drosophila is located close to the C-terminus and is followed by a short stretch of amino acids rich in aspartates and serines.…”

Section: ' End Processing Of Histone Pre-mrnas In Drosophilamentioning

confidence: 99%

Formation of the 3′ end of histone mRNA: Getting closer to the end

Domiński

Marzluff

2007

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Nearly all eukaryotic mRNAs end with a poly (A) tail that is added to their 3' end by the ubiquitous cleavage/polyadenylation machinery. The only known exception to this rule are metazoan replication dependent histone mRNAs, which end with a highly conserved stem-loop structure. This distinct 3' end is generated by specialized 3'end processing machinery that cleaves histone pre-mRNAs 4-5 nucleotides downstream of the stem-loop and consists of the U7 small nuclear RNP (snRNP) and number of protein factors. Recently, the U7 snRNP has been shown to contain a unique Sm core that differs from that of the spliceosomal snRNPs, and an essential heat labile processing factor has been identified as symplekin. In addition, cross-linking studies have pinpointed CPSF-73 as the endonuclease, which catalyzes the cleavage reaction. Thus, many of the critical components of the 3' end processing machinery are now identified. Strikingly, this machinery is not as unique as initially thought but contains a number of factors involved in cleavage/polyadenylation, suggesting that the two mechanisms have a common evolutionary origin. The greatest challenge that lies ahead is to determine how all these factors interact with each other to form a catalytically competent processing complex capable of cleaving histone pre-mRNAs.

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“…Although no such functions of ABCE1 are currently described, several proteins involved in chromatin assembly and remodeling (e.g., SUPT16H, SMARCA5, CBX3 and CBX5) as well as in DNA replication and repair (e.g., RFC4, MMS19) were recently identified among the putative ABCE1 interactors. 34,82 A disruption of SLBP, a central regulator of histone mRNA metabolism, is deleterious for embryonic development of several organisms, resulting in chromosome condensation defect in Drosophila and C. elegans 83,84 and DNA replication failure in mouse oocytes. 85 Human somatic cells with depleted SLBP are viable, although their growth rate is significantly impaired due to a delayed progression through S phase as a result of inefficient DNA synthesis, [52][53][54] thus producing a similar phenotype as ABCE1 silencing in our study.…”

Section: Discussionmentioning

confidence: 99%

ABCE1 is essential for S phase progression in human cells

et al. 2016

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ABCE1 is a highly conserved protein universally present in eukaryotes and archaea, which is crucial for the viability of different organisms. First identified as RNase L inhibitor, ABCE1 is currently recognized as an essential translation factor involved in several stages of eukaryotic translation and ribosome biogenesis. The nature of vital functions of ABCE1, however, remains unexplained. Here, we study the role of ABCE1 in human cell proliferation and its possible connection to translation. We show that ABCE1 depletion by siRNA results in a decreased rate of cell growth due to accumulation of cells in S phase, which is accompanied by inefficient DNA synthesis and reduced histone mRNA and protein levels. We infer that in addition to the role in general translation, ABCE1 is involved in histone biosynthesis and DNA replication and therefore is essential for normal S phase progression. In addition, we analyze whether ABCE1 is implicated in transcript-specific translation via its association with the eIF3 complex subunits known to control the synthesis of cell proliferation-related proteins. The expression levels of a few such targets regulated by eIF3A, however, were not consistently affected by ABCE1 depletion.

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Drosophilastem loop binding protein coordinates accumulation of mature histone mRNA with cell cycle progression

Cited by 129 publications

References 63 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

Formation of the 3′ end of histone mRNA: Getting closer to the end

ABCE1 is essential for S phase progression in human cells

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