Alternative splicing: combinatorial output from the genome

Roberts, G. C.; Smith, Christopher W.

doi:10.1016/s1367-5931(02)00320-4

Cited by 123 publications

(58 citation statements)

References 60 publications

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“…How can the human genome, with only the approximately 25,000 protein-coding genes [2], encode enough diverse proteins to achieve the high level of complexity to ensure, for example, that individual neurons are precisely "wired" with many others and that their functions are finely tuned? It is now clear that protein diversity can be greatly increased through alternative pre-mRNA splicing [3][4][5]. This is a particularly common way for the regulation of gene expression among neuronal genes and likely contributes to the fine-tuning of neuronal functions [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Control of alternative pre-mRNA splicing by Ca++ signals

Xie¹

2008

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Alternative pre-mRNA splicing is a common way of gene expression regulation in metazoans. The selective use of specific exons can be modulated in response to various manipulations that alter Ca ++ signals, particularly in neurons. A number of splicing factors have also been found to be controlled by Ca ++ signals. Moreover, pre-mRNA elements have been identified that are essential and sufficient to mediate Ca ++ -regulated splicing, providing model systems for dissecting the involved molecular components. In neurons, this regulation likely contributes to the fine-tuning of neuronal properties.

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Section: Introductionmentioning

confidence: 99%

Control of alternative pre-mRNA splicing by Ca++ signals

Xie¹

2008

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…In up to 60% of human genes, at least one alternatively spliced isoform has been identified. 16,33 The aim of this study was to investigate potential splice isoforms of the cell cycle regulator cyclin E1 in well-established mouse models of hepatocarcinogenesis and liver regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11] Several reports have shown that overexpression of cyclin E1 accelerates G1 phase, decreases size of mitotic cells, promotes cell division independent from growth factors, and causes chromosomal instability in cancer cells. [12][13][14][15] Alternative splicing occurs in 60% of human genes 16 and modulates the oncogenic functions of BRCA1 and BRCA2 in breast cancer or Bcl2 in prostate cancer. 17,18 Several alternative spliced variants of human cyclin E1 have been isolated that modify cyclin function.…”

Section: Uring Cell Division In Eukaryotic Cells Cyclin E1mentioning

confidence: 99%

Expression of a cyclin E1 isoform in mice is correlated with the quiescent cell cycle status of hepatocytes in vivo

et al. 2006

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Cyclin E1 controls G1/S phase transition of the eukaryotic cell cycle. We report the impact of alternative spliced cyclin E1 isoforms on cell cycle regulation in hepatocytes. We show that expression of new cyclin E1 mRNA variants IN3, ⌬4, and ⌬5 is associated with retarded proliferation in murine hepatocellular carcinoma. Additionally, we demonstrate that a new cyclin E1 isoform ⌬3/8 lacking the central part of wild-type mRNA is expressed predominantly in nonproliferating murine hepatocytes. Following partial hepatectomy, ⌬3/8 is downregulated when hepatocytes enter the cell cycle from quiescence. The ⌬3/8 protein does not exhibit any cyclin box motif but binds cyclin-dependent kinase 2 without stimulating kinase activity. We demonstrate that ⌬3/8 lacks any nuclear localization signal and is exclusively located in the cytoplasm. Overexpression of ⌬3/8 in cultured cells leads to a delayed G0-G1 transition, indicating that this splice variant helps to maintain a quiescent state of hepatocytes. In conclusion, we identified an isoform of cyclin E1 involved in G0 maintenance and suggest an additional mechanism for cell cycle control. ( D uring cell division in eukaryotic cells, cyclin E1 expression oscillates with a peak at G1/S phase transition. To coordinate progression of the cell cycle, cyclin E1 forms complexes with and controls kinase activity of cyclin-dependent kinase 2 (cdk2). 1-3 Thus, cyclin E1-cdk2 complexes phosphorylate substrates essential for a synchronized initiation of DNA replication, centrosome duplication, chromatin remodeling, and histone biogenesis at G1/S phase transition. 4 Moreover, in adult hepatocytes cyclin E1 plays an important role in cell cycle regulation. After partial hepatectomy (PH) in mice, cyclin E1 expression increases and peaks at 36 hours after resection, which reflects the increasing number of dividing hepatocytes. 5,6 Therefore, cyclin E1 is used as a marker to monitor cell cycle progression during liver regeneration.Dysregulated cyclin E1 expression has been shown to act as a potent oncogene in some types of human cancer. Amplification of the cyclin E1 gene and cell cycle-independent overexpression promotes tumor development, particularly in breast cancer but also in hepatocellular carcinoma (HCC). [7][8][9][10][11] Several reports have shown that overexpression of cyclin E1 accelerates G1 phase, decreases size of mitotic cells, promotes cell division independent from growth factors, and causes chromosomal instability in cancer cells. [12][13][14][15] Alternative splicing occurs in 60% of human genes 16 and modulates the oncogenic functions of BRCA1 and BRCA2 in breast cancer or Bcl2 in prostate cancer. 17,18 Several alternative spliced variants of human cyclin E1 have been isolated that modify cyclin function. [19][20][21] The biological functions of cyclin E1 alternative splice variants during cell cycle of normal or malignant cells are widely unknown.

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“…Des algorithmes spécifiques ont été développés et plusieurs approches expérimentales à haut débit ont été explorées (Figure 4). L'utilisation de sondes oligonucléotidiques fixées sur des filtres de forte densité a permis l'hybridation d'ARNm à des taux reflétant la spécificité tissulaire d'expression des gènes cibles [15]. Des méthodes plus sophistiquées utilisant des fibres optiques ont également été proposées [16].…”

Section: Identification Des éVénements D'épissage Alternatifunclassified

Épissage alternatif, pathologie et thérapeutique moléculaire

Corcos

Solier

2005

Med Sci (Paris)

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Alternative splicing: combinatorial output from the genome

Cited by 123 publications

References 60 publications

Control of alternative pre-mRNA splicing by Ca++ signals

Control of alternative pre-mRNA splicing by Ca++ signals

Expression of a cyclin E1 isoform in mice is correlated with the quiescent cell cycle status of hepatocytes in vivo

Épissage alternatif, pathologie et thérapeutique moléculaire

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