Expression of human snRNA genes from beginning to end

Egloff, Sylvain; O’Reilly, Dawn; Murphy, Shona

doi:10.1042/bst0360590

Cited by 97 publications

(101 citation statements)

References 34 publications

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“…Other major RNAPII transcribed genes producing transcripts <500 nt are snRNA loci (U1, U2, U4, U5, U11, U12, and U4atac) (Montzka and Steitz 1988;Jawdekar and Henry 2008) and loci producing the independently transcribed and capped snoRNAs (U3, U8, and U13). These genes also have specialized 39 end processing/ transcription termination systems (Kim et al 2006;Egloff et al 2008).…”

Section: Short Genes Use Pa Site-independent Terminatorsmentioning

confidence: 99%

Promoter-proximal polyadenylation sites reduce transcription activity

2012

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Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within~500 base pairs of the promoter. In contrast, promoter-proximal positioning of a pA site-independent histone gene terminator supports high transcription levels. We propose that optimal communication between a pA site-dependent gene terminator and its promoter critically depends on gene length and that short RNA polymerase II-transcribed genes use specialized termination mechanisms to maintain high transcription levels.

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Section: Short Genes Use Pa Site-independent Terminatorsmentioning

confidence: 99%

Promoter-proximal polyadenylation sites reduce transcription activity

2012

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“…We therefore constructed a reporter gene that relies on a promoter derived from the Drosophila U7 snRNA gene. snRNA genes associate with a distinct set of transcriptional factors, and primary transcripts generated from these genes (pre-snRNAs) are cleaved at the 3 ′ end by a distinct machinery termed Integrator that shares no common components with the two types of 3 ′ -end processing machineries operating on premRNAs (Baillat et al 2005;Egloff et al 2008;Ezzeddine et al 2011).…”

Section: Components Of the Hcc Essential Formentioning

confidence: 99%

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

Sabath

Skrajna

Yang

et al. 2013

RNA

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3′ -End cleavage of animal replication-dependent histone pre-mRNAs is controlled by the U7 snRNP. Lsm11, the largest component of the U7-specific Sm ring, interacts with FLASH, and in mammalian nuclear extracts these two proteins form a platform that recruits the CPSF73 endonuclease and other polyadenylation factors to the U7 snRNP. FLASH is limiting, and the majority of the U7 snRNP in mammalian extracts exists as a core particle consisting of the U7 snRNA and the Sm ring. Here, we purified the U7 snRNP from Drosophila nuclear extracts and characterized its composition by mass spectrometry. In contrast to the mammalian U7 snRNP, a significant fraction of the Drosophila U7 snRNP contains endogenous FLASH and at least six subunits of the polyadenylation machinery: symplekin, CPSF73, CPSF100, CPSF160, WDR33, and CstF64. The same composite U7 snRNP is recruited to histone pre-mRNA for 3 ′ -end processing. We identified a motif in Drosophila FLASH that is essential for the recruitment of the polyadenylation complex to the U7 snRNP and analyzed the role of other factors, including SLBP and Ars2, in 3 ′ -end processing of Drosophila histone pre-mRNAs. SLBP that binds the upstream stem-loop structure likely recruits a yet-unidentified essential component(s) to the processing machinery. In contrast, Ars2, a protein previously shown to interact with FLASH in mammalian cells, is dispensable for processing in Drosophila. Our studies also demonstrate that Drosophila symplekin and three factors involved in cleavage and polyadenylation-CPSF, CstF, and CF I m -are present in Drosophila nuclear extracts in a stable supercomplex.

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“…These include the multisubunit transcription factor PTF/PBP/SNAPc (PSEbinding transcription factor/PSE-binding protein/snRNA-activating protein complex), which recognizes the PSE element located ;50 bp upstream of the transcription start site, and pol II phosphorylated on serine 7 (Ser7) of the carboxy-terminal domain (CTD) heptapeptide (Egloff et al 2008). In addition, we used antibodies to pol II and acetylated H3 core histone proteins, which are primarily associated with promoter regions of actively transcribing genes (Shahbazian and Grunstein 2007).…”

Section: U1 Snrna Class I Pseudogenes Are Transcriptionally Active Inmentioning

confidence: 99%

Differentially expressed, variant U1 snRNAs regulate gene expression in human cells

et al. 2012

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Human U1 small nuclear (sn)RNA, required for splicing of pre-mRNA, is encoded by genes on chromosome 1 (1p36). Imperfect copies of these U1 snRNA genes, also located on chromosome 1 (1q12-21), were thought to be pseudogenes. However, many of these “variant” (v)U1 snRNA genes produce fully processed transcripts. Using antisense oligonucleotides to block the activity of a specific vU1 snRNA in HeLa cells, we have identified global transcriptome changes following interrogation of the Affymetrix Human Exon ST 1.0 array. Our results indicate that this vU1 snRNA regulates expression of a subset of target genes at the level of pre-mRNA processing. This is the first indication that variant U1 snRNAs have a biological function in vivo. Furthermore, some vU1 snRNAs are packaged into unique ribonucleoproteins (RNPs), and many vU1 snRNA genes are differentially expressed in human embryonic stem cells (hESCs) and HeLa cells, suggesting developmental control of RNA processing through expression of different sets of vU1 snRNPs.

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Expression of human snRNA genes from beginning to end

Cited by 97 publications

References 34 publications

Promoter-proximal polyadenylation sites reduce transcription activity

Promoter-proximal polyadenylation sites reduce transcription activity

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

Differentially expressed, variant U1 snRNAs regulate gene expression in human cells

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