Transcriptional termination sequences in the mouse serum albumin gene

West, Steven; Zaret, Kenneth S.; Proudfoot, Nick J.

doi:10.1261/rna.2232406

Cited by 18 publications

(28 citation statements)

References 37 publications

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“…The modification decreases in what is sometimes more of a stepwise than a continuous fashion near or beyond the end of the gene, often near the site of cleavage and polyadenylation, and some distance upstream of the furthest regions where RNA polymerase serine 2 phosphorylation can be detected. This is consistent with models for multiple transcription termination signals in the DNA that are not closely linked to the site of polyadenylation (West et al 2006), in addition to effects of the polyadenylation signals on RNA polymerase pausing or termination. They also indicate that either demethylation becomes more active or KMT3 becomes less active prior to removal of the RNA polymerase from the DNA template.…”

Section: Discussionsupporting

confidence: 86%

“…Studies of nascent transcripts in a few selected highly transcribed loci have shown that transcription may proceed well beyond the site of poly(A) addition, supporting a model in which elongated transcripts are cleaved at poly(A) addition sites (for review, see West et al 2006) and the remaining 3Ј ends of the transcripts degraded by mechanisms that are still under study. The presence of an accessible polyadenylation signal (AAUAAA in this case) was found to be necessary for efficient transcription termination (Nag et al 2006) and transcription termination without precursor RNA cleavage has been observed in vivo in Drosophila (Osheim et al 2002) as well as in vitro.…”

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confidence: 78%

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A genomic analysis of RNA polymerase II modification and chromatin architecture related to 3′ end RNA polyadenylation

Zheng

Karpikov²,

Jin³

et al. 2008

Genome Res.

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Genomic analyses have been applied extensively to analyze the process of transcription initiation in mammalian cells, but less to transcript 3Ј end formation and transcription termination. We used a novel approach to prepare 3Ј end fragments from polyadenylated RNA, and mapped the position of the poly(A) addition site using oligonucleotide arrays tiling 1% of the human genome. This approach revealed more 3Ј ends than had been annotated. The distribution of these ends relative to RNA polymerase II (PolII) and di-and trimethylated lysine 4 and lysine 36 of histone H3 was compared. A substantial fraction of unannotated 3Ј ends of RNA are intronic and antisense to the embedding gene. Poly(A) ends of annotated messages lie on average 2 kb upstream of the end of PolII binding (termination). Near the termination sites, and in some internal sites, unphosphorylated and C-terminal domain (CTD) serine 2 phosphorylated PolII (POLR2A) accumulate, suggesting pausing of the polymerase and perhaps dephosphorylation prior to release. Lysine 36 trimethylation occurs across transcribed genes, sometimes alternating with stretches of DNA in which lysine 36 dimethylation is more prominent. Lysine 36 methylation decreases at or near the site of polyadenylation, sometimes disappearing before disappearance of phosphorylated RNA PolII or release of PolII from DNA. Our results suggest that transcription termination loss of histone 3 lysine 36 methylation and later release of RNA polymerase. The latter is often associated with polymerase pausing. Overall, our study reveals extensive sites of poly(A) addition and provides insights into the events that occur during 3Ј end formation.

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Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 78%

A genomic analysis of RNA polymerase II modification and chromatin architecture related to 3′ end RNA polyadenylation

Zheng

Karpikov²,

Jin³

et al. 2008

Genome Res.

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“…The strong signal over B3 observed in all three constructs is due to polymerases from this region transcribing into the B4 selection region during the NRO transcription reaction. Signals immediately upstream of the selection probe are routinely observed in hybrid selection NRO analysis (8,33). Overall, these results show that there is no detectable CoTC activity associated with transcripts from the MAZ 4 insert.…”

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confidence: 65%

Pause Sites Promote Transcriptional Termination of Mammalian RNA Polymerase II

Gromak

West

Proudfoot

2006

Molecular and Cellular Biology

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161

167

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Polymerase II (Pol II) transcriptional termination depends on two independent genetic elements: poly(A) signals and downstream terminator sequences. The latter may either promote cotranscriptional RNA cleavage or pause elongating Pol II. We demonstrate that the previously characterized MAZ 4 pause element promotes Pol II termination downstream of a poly(A) signal, dependent on both the proximity of the pause site and poly(A) signal and the strength of the poly(A) signal. The 533 exonuclease Xrn2 facilitates this pausedependent termination by degrading the 3 product of poly(A) site cleavage. The human ␤-actin gene also possesses poly(A) site proximal pause sequences, which like MAZ 4 are G rich and promote transcriptional termination. Xrn2 depletion causes an increase in both steady-state RNA and Pol II levels downstream of the ␤-actin poly(A) site. Taken together, we provide new insights into the mechanism of pause site-mediated termination and establish a general role for the 533 exonuclease Xrn2 in Pol II termination.Transcriptional termination can be defined as cessation of RNA synthesis followed by polymerase-DNA dissociation. Correct termination serves to maintain an active cellular pool of RNA polymerase II (Pol II) and to insulate downstream promoters from elongating Pol II (11). Despite the fundamental importance of this process, its mechanism remains enigmatic. Transcripts of all protein-encoding genes, with the exception of histone genes, contain a poly(A) signal at their 3Ј end composed of an AAUAAA sequence positioned 10 to 50 nucleotides upstream of a GU-rich downstream sequence element (see references 20 and 38 for reviews). The 5Ј product of endonucleolytic cleavage between these two sequences is polyadenylated and therefore stabilized. The 3Ј product of the cleavage is unstable and rapidly degraded.A substantial body of evidence argues that cleavage and polyadenylation of Pol II transcripts occur cotranscriptionally, effectively releasing mRNA from the transcription site. Thus, defects in mRNA 3Ј-end processing cause the accumulation of pre-mRNA at nuclear transcription foci both in yeast (13) and in mammals (6). Furthermore, numerous studies have shown that the C-terminal domain of the Pol II large subunit promotes efficient cleavage and polyadenylation (see references 14, 18, and 21 for reviews). It is also well documented that for mRNAs with multiple poly(A) signals, selection of a downstream poly(A) site results in mRNA with internal unprocessed poly(A) signals (7, 10). If 3Ј processing occurred posttranscriptionally, then usage of upstream poly(A) signals would always predominate. Finally, the poly(A) site is necessary for efficient transcriptional termination. However, the site of Pol II release is often distinct from the gene's poly(A) site. Thus, Pol II terminates transcription at sites positioned between 100 bp and several kb downstream of the poly(A) site (2,8,10,12,29). These observations suggest a requirement for additional, distal sequences in the termination process.A sequence (G 5 ...

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“…Another sequence, a CCAAT-box in the adenovirus late promoter is necessary for termination of the upstream gene (Connelly and Manley 1989). West et al (2006b) showed that multiple termination sequence elements in the mouse serum albumin (MSA) 39-flanking region promote termination. Many MSA transcripts appear to be cleaved cotranscriptionally and, interestingly, seem to be adenylated and processed by the TRAMP/exosome complex (West et al 2006a,b).…”

Section: Pausing the Polymerase: Another Factor In Rnapii Terminationmentioning

confidence: 99%

Transcription termination by nuclear RNA polymerases

Richard

Manley²

2009

Genes Dev.

289

326

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Gene transcription in the cell nucleus is a complex and highly regulated process. Transcription in eukaryotes requires three distinct RNA polymerases, each of which employs its own mechanisms for initiation, elongation, and termination. Termination mechanisms vary considerably, ranging from relatively simple to exceptionally complex. In this review, we describe the present state of knowledge on how each of the three RNA polymerases terminates and how mechanisms are conserved, or vary, from yeast to human.

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Transcriptional termination sequences in the mouse serum albumin gene

Cited by 18 publications

References 37 publications

A genomic analysis of RNA polymerase II modification and chromatin architecture related to 3′ end RNA polyadenylation

A genomic analysis of RNA polymerase II modification and chromatin architecture related to 3′ end RNA polyadenylation

Pause Sites Promote Transcriptional Termination of Mammalian RNA Polymerase II

Transcription termination by nuclear RNA polymerases

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