Structural organization and chromosome location of the mouse Elongin A gene (&lt;i&gt;Tceb3&lt;/i&gt;)

Aso, Teijiro; Amimoto, Keiko; Takebayashi, Shin‐ichiro; Okumura, Katsuhiko; Hatakeyama, Masanori

doi:10.1159/000015355

Cited by 6 publications

(8 citation statements)

References 13 publications

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“…As shown in Fig. 2, the Elongin A3 probe hybridized to a single band of ϳ5.0 kb and, consistent with previous studies, the Elongin A-specific probe hybridized to two mRNA species of ϳ5.2 and ϳ2.8 kb (10,28). To correct for the amount of RNA loaded in each lane, we measured the intensity of each of the bands on the blot after the hybridization with the ␤-actin probe.…”

Section: Resultssupporting

confidence: 83%

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Identification and Biochemical Characterization of a Novel Transcription Elongation Factor, Elongin A3

Yamazaki¹,

Guo²,

Sugahara³

et al. 2002

Journal of Biological Chemistry

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The Elongin complex stimulates the rate of transcription elongation by RNA polymerase II by suppressing the transient pausing of the polymerase at many sites along the DNA template. Elongin is composed of a transcriptionally active A subunit and two small regulatory B and C subunits, the latter binding stably to each other to form a binary complex that interacts with Elongin A and strongly induces its transcriptional activity. To further understand the role of Elongin A in transcriptional regulation by RNA polymerase II, we are attempting to identify Elongin A-related proteins. Here, we report on the molecular cloning, expression, and biochemical characterization of human Elongin A3, a novel transcription elongation factor that exhibits 49 and 81% identity to Elongin A and the recently identified Elongin A2, respectively. The mRNA of Elongin A3 is ubiquitously expressed, and the protein is localized to the nucleus of cells. Mechanistic studies have demonstrated that Elongin A3 possesses similar biochemical features to Elongin A2. Both stimulate the rate of transcription elongation by RNA polymerase II and are capable of forming a stable complex with Elongin BC. In contrast to Elongin A, however, their transcriptional activities are not activated by Elongin BC. Structure-function analyses using fusion proteins composed of Elongin A3 and Elongin A revealed that the COOH-terminal region of Elongin A is important for the activation by Elongin BC.The synthesis of messenger RNA in eukaryotes is a complex biochemical process controlled by the concerted action of a set of general transcription factors that regulate the activity of RNA polymerase II during the initiation and elongation stages of transcription. At least six general transcription initiation factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH) 1 have been identified in eukaryotic cells and found to promote the selective binding of RNA polymerase II to promoters and to support a basal level of transcription (1). In addition to the general initiation factors, at least 16 elongation factors have been defined biochemically and found to increase the efficiency of transcription elongation by RNA polymerase II (2-5).Among the elongation factors, SII and P-TEFb prevent RNA polymerase II from prematurely arresting transcription. SII does this by promoting passage of the polymerase through a variety of transcriptional impediments, including DNA sequences that act as intrinsic arrest sites and DNA-bound proteins and drugs (6). P-TEFb catalyzes the conversion of early, termination-prone elongation complexes into productive elongation complexes (7). The rest of the elongation factors such as TFIIF (8), Elongin A (9), Elongin A2 (10), ELL (11), and the Cockayne syndrome group B protein (CSB) (12), act to increase the overall rate of RNA chain elongation by RNA polymerase II by decreasing the frequency and/or duration of transient pausing of the polymerase at sites along the DNA template.Elongin was initially identified as a heterotrimer composed of A, B, and C subunits...

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Section: Resultssupporting

confidence: 83%

“…What is the mechanism by which Elongin A is activated by (10,28,(31)(32)(33). It has also been reported that Elongin A is predominantly localized in the nucleus (25,34).…”

Section: Fig 3 Elongin A3 Forms a Complex With Elongins B And C Amentioning

confidence: 97%

Identification and Biochemical Characterization of a Novel Transcription Elongation Factor, Elongin A3

Yamazaki¹,

Guo²,

Sugahara³

et al. 2002

Journal of Biological Chemistry

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“…We first isolated and analyzed the structure of the mouse Elongin A gene (19). A gene-targeting vector was then constructed by replacing exons 8 -10 of the Elongin A gene, which encode the domain essential for its transcriptional elongation activity (15), with a pol II-neo-poly(A) cassette (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Clones-A 15-kb genomic fragment spanning the sequence encoding exons 2-11 and the 3Ј-UTR of murine Elongin A was isolated from a 129/Sv mouse genomic library, using a mouse Elongin A cDNA probe (19). Genomic fragments of 4.5 and 1.4 kb flanking exons 8 -10 of Elongin A were used to generate a targeting construct in which exons 8 -10 were replaced by a pol II-neo-poly(A) cassette (20).…”

Section: Generation Of the Elongin A-deficient Es Cellmentioning

confidence: 99%

Mammalian Elongin A Is Not Essential for Cell Viability but Is Required for Proper Cell Cycle Progression with Limited Alteration of Gene Expression

Yamazaki

Aso

Ohnishi

et al. 2003

Journal of Biological Chemistry

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(pol II) 1 is regulated by the concerted action of a set of general transcription factors that control the activity of pol II during the initiation and elongation stages of transcription. At least six general transcription initiation factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH) have been identified in eukaryotic cells and found to promote the selective binding of pol II to promoters and to support a basal level of transcription (1). In addition to the general initiation factors, at least 17 elongation factors have been defined biochemically and found to promote efficient elongation of transcripts by pol II (2-5). These elongation factors fall into two broad functional classes based on their abilities to either reactivate arrested pol II or suppress transient pausing of pol II. The first class is solely composed of SII (6). The rest of the elongation factors, including TFIIF (7), Elongin A (8), Elongin A2 (9), Elongin A3 (10), and Cockayne syndrome B (CSB) protein (11), all act to increase the overall rate of mRNA chain elongation by decreasing the frequency and/or duration of transient pausing of pol II at sites along the DNA template.

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“…19 To examine whether Elongin A is expressed when such lethality occurs, we analyzed its expression at different developmental stages in wild-type (WT) embryos. A high level of Elongin A mRNA was detected in E4.5 embryos and was thereafter sustained throughout embryogenesis (Figure 1d), suggesting that Elongin A plays a critical role in embryonic development.…”

Section: Resultsmentioning

confidence: 99%

Induction of apoptosis and cellular senescence in mice lacking transcription elongation factor, Elongin A

et al. 2006

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Elongin A is a transcription elongation factor that increases the overall rate of mRNA chain elongation by RNA polymerase II. To gain more insight into the physiological functions of Elongin A, we generated Elongin A-deficient mice. Elongin A homozygous mutant (Elongin A À/À ) embryos demonstrated a severely retarded development and died at between days 10.5 and 12.5 of gestation, most likely due to extensive apoptosis. Moreover, mouse embryonic fibroblasts (MEFs) derived from Elongin A À/À embryos exhibited not only increased apoptosis but also senescence-like growth defects accompanied by the activation of p38 MAPK and p53. Knockdown of Elongin A in MEFs by RNA interference also dramatically induced the senescent phenotype. A study using inhibitors of p38 MAPK and p53 and the generation of Elongin A-deficient mice with p53-null background suggests that both the p38 MAPK and p53 pathways are responsible for the induction of senescence-like phenotypes, whereas additional signaling pathways appear to be involved in the mediation of apoptosis in Elongin A À/À cells. Taken together, our results suggest that Elongin A is required for the transcription of genes essential for early embryonic development and downregulation of its activity is tightly associated with cellular senescence. Cell Death and Differentiation (2007) Eukaryotic mRNA synthesis by RNA polymerase II (pol II) is regulated by the concerted action of a set of transcription factors that control the activity of pol II during the initiation and elongation stages of transcription. At least six general transcription factors have been identified in eukaryotic cells and found to promote the selective binding of pol II to promoters and to support the basal level of transcription. 1 In addition, a diverse collection of elongation factors that promote efficient elongation of transcripts by pol II in vitro have also been identified. 2-4 These factors fall into two broad functional classes based on their ability to either reactivate arrested pol II or suppress the transient pausing of pol II. The first class is composed of members of the SII family. 3,5 The second class comprises a collection of elongation factors, including TFIIF, 6 Elongin, 7,8 ELL 9 and CSB, 10 which increase the overall rate of mRNA chain elongation by decreasing the frequency and/or duration of transient pausing of pol II at sites along the DNA template.Elongin was identified as a heterotrimer composed of A, B and C subunits of B770, 118 and 112 amino acids, respectively. 7,8,11,12 Elongin A is the transcriptionally active subunit, whereas Elongins B and C are positive regulatory subunits that can form an isolable Elongin BC subcomplex. 8,13,14 Although the functions of Elongin A in vivo remain largely unclear, Gerber et al. 15 have recently reported that the Drosophila homolog of Elongin A (dEloA) colocalizes with pol II at sites of active transcription on polytene chromosomes, and it also plays a critical role in heat shock gene expression in vivo. 15,16 Moreover, by the RNA interference (...

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Structural organization and chromosome location of the mouse Elongin A gene (<i>Tceb3</i>)

Cited by 6 publications

References 13 publications

Identification and Biochemical Characterization of a Novel Transcription Elongation Factor, Elongin A3

Identification and Biochemical Characterization of a Novel Transcription Elongation Factor, Elongin A3

Mammalian Elongin A Is Not Essential for Cell Viability but Is Required for Proper Cell Cycle Progression with Limited Alteration of Gene Expression

Induction of apoptosis and cellular senescence in mice lacking transcription elongation factor, Elongin A

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