Distinct self-interaction domains promote Multi Sex Combs accumulation in and formation of the<i>Drosophila</i>histone locus body

Terzo, Esteban A.; Lyons, Shawn M.; Poulton, Joanna; Temple, Brenda; Marzluff, William F.; Duronio, Robert J.

doi:10.1091/mbc.e14-10-1445

Cited by 36 publications

(85 citation statements)

References 76 publications

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“…The HLB creates an optimal environment for efficient transcription and histone pre-mRNA processing (3′-end formation) by concentrating factors necessary for histone mRNA biogenesis [7]. Formation of the HLB requires nuclear protein at the ataxia-telangiectasia locus (NPAT; Mxc in Drosophila ) which is essential for the expression of all five classes of histone genes [8,9]. FLICE-associated huge protein (FLASH) and U7 small nuclear ribonucleoprotein (U7 snRNP), both of which are required for processing, are also found in the HLB.…”

Section: Replication-dependent Histone Mrnas: a Novel Set Of Cell Cycmentioning

confidence: 99%

Birth and Death of Histone mRNAs

2017

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In metazoans, histone mRNAs are not polyadenylated but end in a conserved stem-loop. Stem-loop binding protein (SLBP) binds to the stem-loop and is required for all steps in histone mRNA metabolism. The genes for the five histone proteins are linked. A histone locus body (HLB) forms at each histone gene locus. It contains factors essential for transcription and processing of histone mRNAs, and couples transcription and processing. The active form of U7 snRNP contains the HLB component FLASH (FLICE-associated huge protein), the histone cleavage complex (HCC), and a subset of polyadenylation factors including the endonuclease CPSF73. Histone mRNAs are rapidly degraded when DNA replication is inhibited by a 3′ to 5′ pathway that requires extensive uridylation of mRNA decay intermediates.

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Section: Replication-dependent Histone Mrnas: a Novel Set Of Cell Cycmentioning

confidence: 99%

Birth and Death of Histone mRNAs

2017

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“…69 Drosophila Mxc and mammalian NPAT contain a conserved N-terminal LisH domain and an adjacent SIF (self-interaction facilitator) domain that in Drosophila mediate self-interaction among Mxc molecules. 70 The LisH and SIF domains of Mxc do not mediate simple dimerization, but instead provide multivalent binding capability that could help oligomerize Mxc into a large molecular network that provides a scaffold for the recruitment of other HLB components (Fig. 3).…”

Section: Self-organization Of the Hlbmentioning

confidence: 99%

“…Importantly, the oligomerization mediated by the LisH and SIF domains is required for Mxc function in vivo, as substitution mutations of 3 amino acids in either domain render Mxc completely unable to support HLB assembly and are lethal. 70 The LisH of NPAT domain is necessary for NPAT to stimulate histone gene expression. 33 However, an ectopically expressed NPAT lacking the LisH domain can localize to the HLB, perhaps because other domains can interact with endogenous, wild type NPAT at the HLB.…”

Section: Self-organization Of the Hlbmentioning

confidence: 99%

“…For instance, an N-terminal fragment of Mxc containing the LisH and SIF domains that is unable to support HLB formation or transcription on its own is nonetheless able to concentrate in the HLB in the presence of wild type Mxc, likely both by selfassociating and interacting with endogenous full length Mxc within the HLB. 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.…”

Section: Self-organization Of the Hlbmentioning

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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Distinct self-interaction domains promote Multi Sex Combs accumulation in and formation of theDrosophilahistone locus body

Cited by 36 publications

References 76 publications

Birth and Death of Histone mRNAs

Birth and Death of Histone mRNAs

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

Coordinating transcription and replication to mitigate their conflicts in early Drosophila embryos

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