3′-End processing of histone pre-mRNAs in <i>Drosophila</i>: U7 snRNP is associated with FLASH and polyadenylation factors

Sabath, Ivan; Skrajna, Aleksandra; Yang, Xiao Cui; Dadlez, Michał; Marzluff, William F.; Domiński, Zbigniew

doi:10.1261/rna.040360.113

Cited by 49 publications

(93 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Drosophila, there is no histone pre-mRNA cleavage until dSLBP binds (10). The free phosphorylated C-terminal tail of dSLBP could assist in assembling a processing complex after it has promoted binding to the stemloop RNA.…”

Section: Discussionmentioning

confidence: 99%

“…In mammalian nuclear extracts, SLBP is not absolutely required for the biochemical reaction of processing (12). In contrast, cleavage of histone pre-mRNA in Drosophila cells and nuclear extracts requires the binding of SLBP to the stem loop (10,13).…”

mentioning

confidence: 97%

“…Other factors, including the endonuclease CPSF-73, are involved in both polyadenylation and histone mRNA 3′-end processing (8)(9)(10)(11). In mammalian nuclear extracts, SLBP is not absolutely required for the biochemical reaction of processing (12).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Molecular mechanisms for the regulation of histone mRNA stem-loop–binding protein by phosphorylation

Zhang

Tan

DeRose

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Replication-dependent histone mRNAs end with a conserved stem loop that is recognized by stem-loop-binding protein (SLBP). The minimal RNA-processing domain of SLBP is phosphorylated at an internal threonine, and Drosophila SLBP (dSLBP) also is phosphorylated at four serines in its 18-aa C-terminal tail. We show that phosphorylation of dSLBP increases RNA-binding affinity dramatically, and we use structural and biophysical analyses of dSLBP and a crystal structure of human SLBP phosphorylated on the internal threonine to understand the striking improvement in RNA binding. Together these results suggest that, although the C-terminal tail of dSLBP does not contact the RNA, phosphorylation of the tail promotes SLBP conformations competent for RNA binding and thereby appears to reduce the entropic penalty for the association. Increased negative charge in this C-terminal tail balances positively charged residues, allowing a more compact ensemble of structures in the absence of RNA.X-ray crystallography | NMR | intrinsically disordered protein H istone synthesis increases at the beginning of S-phase to package newly replicated DNA with histone proteins, but synthesis must be shut down rapidly and histone mRNA degraded at the end of DNA replication because of the toxicity of surplus histone proteins (1, 2). This cyclic demand for histones requires strict regulation, which is achieved mainly by controlling the synthesis and degradation of histone mRNA (3). Replication-dependent histone mRNAs are the only known cellular mRNAs that are not polyadenylated and instead end with a conserved stem loop (4). Histone mRNAs are generated from longer histone pre-mRNAs as a result of an endonucleolytic cleavage between the stem loop and a purine-rich downstream sequence termed the "histone downstream element" (HDE) (5).Stem-loop-binding protein (SLBP), also known as "hairpinbinding protein" (6), binds to the histone mRNA stem loop, and U7 small nuclear ribonucleoprotein binds to the HDE (7). Other factors, including the endonuclease CPSF-73, are involved in both polyadenylation and histone mRNA 3′-end processing (8-11). In mammalian nuclear extracts, SLBP is not absolutely required for the biochemical reaction of processing (12). In contrast, cleavage of histone pre-mRNA in Drosophila cells and nuclear extracts requires the binding of SLBP to the stem loop (10, 13).The minimal histone mRNA processing domain of Drosophila SLBP contains a 72-aa RNA-binding domain (RBD) unique to SLBPs and an 18-aa C-terminal region (Fig. 1A) (14). This RNAprocessing domain (RPD) is necessary and sufficient for histone mRNA 3′-end processing in vitro (15). The RBDs of human SLBP (hSLBP) and Drosophila SLBP (dSLBP) are phosphorylated at a Thr residue in a conserved TPNK motif (16,17). The recent crystal structure of hSLBP RBD in complex with histone mRNA stem loop and 3′ hExo, a 3′-5′ exonuclease required for histone mRNA degradation, provided the first molecular insights into the architecture of this complex, and revealed how the hSLBP RBD forms a new ...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

See 1 more Smart Citation

Molecular mechanisms for the regulation of histone mRNA stem-loop–binding protein by phosphorylation

Zhang

Tan

DeRose

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…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%

“…FLASH and Lsm11 interact to form a protein surface that recruits a set of proteins termed the histone cleavage complex (HCC). 100,101 The HCC includes the endonuclease core of the CPSF polyadenylation complex (CPSF73 and CPSF100) plus the protein Symplekin, which binds CstF64. The Symplekin/CstF64 interaction is likely specific for histone pre-mRNA processing, since CstF64 forms a complex with CstF77 and CstF50 that functions in polyadenylation using the same region it uses to interact with Symplekin.…”

Section: Knockdown Of Y3mentioning

confidence: 99%

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

2017

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Coordination of DNA Replication and Histone Synthesis During S Phase

Paik¹,

Giovinazzi²,

Gunjan³

2016

The Initiation of DNA Replication in Eukaryotes

View full text Add to dashboard Cite

3′-End processing of histone pre-mRNAs in Drosophila: U7 snRNP is associated with FLASH and polyadenylation factors

Cited by 49 publications

References 69 publications

Molecular mechanisms for the regulation of histone mRNA stem-loop–binding protein by phosphorylation

Molecular mechanisms for the regulation of histone mRNA stem-loop–binding protein by phosphorylation

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

Coordination of DNA Replication and Histone Synthesis During S Phase

Contact Info

Product

Resources

About