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  • 1
    Publication Date: 2016-04-08
    Description: The RNase P-mediated endonucleolytic cleavage plays a crucial role in the 3' end processing and cellular accumulation of MALAT1, a nuclear-retained long noncoding RNA that promotes malignancy. The regulation of this cleavage event is largely undetermined. Here we characterize a broadly expressed natural antisense transcript at the MALAT1 locus, designated as TALAM1, that positively regulates MALAT1 levels by promoting the 3' end cleavage and maturation of MALAT1 RNA. TALAM1 RNA preferentially localizes at the site of transcription, and also interacts with MALAT1 RNA. Depletion of TALAM1 leads to defects in the 3' end cleavage reaction and compromises cellular accumulation of MALAT1. Conversely, overexpression of TALAM1 facilitates the cleavage reaction in trans . Interestingly, TALAM1 is also positively regulated by MALAT1 at the level of both transcription and RNA stability. Together, our data demonstrate a novel feed-forward positive regulatory loop that is established to maintain the high cellular levels of MALAT1, and also unravel the existence of sense-antisense mediated regulatory mechanism for cellular lncRNAs that display RNase P-mediated 3' end processing.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2002-08-10
    Description: Origin recognition complex (ORC) proteins serve as a landing pad for the assembly of a multiprotein prereplicative complex, which is required to initiate DNA replication. During mitosis, the smallest subunit of human ORC, Orc6, localizes to kinetochores and to a reticular-like structure around the cell periphery. As chromosomes segregate during anaphase, the reticular structures align along the plane of cell division and some Orc6 localizes to the midbody before cells separate. Silencing of Orc6 expression by small interfering RNA (siRNA) resulted in cells with multipolar spindles, aberrant mitosis, formation of multinucleated cells, and decreased DNA replication. Prolonged periods of Orc6 depletion caused a decrease in cell proliferation and increased cell death. These results implicate Orc6 as an essential gene that coordinates chromosome replication and segregation with cytokinesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prasanth, Supriya G -- Prasanth, Kannanganattu V -- Stillman, Bruce -- CA13106/CA/NCI NIH HHS/ -- P01 CA013106/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Aug 9;297(5583):1026-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12169736" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bromodeoxyuridine/metabolism ; Cell Death ; *Cell Division ; Cell Line ; Cell Nucleus/metabolism ; Cells, Cultured ; Centromere/metabolism ; *Chromosome Segregation ; Chromosomes, Human/*metabolism ; *DNA Replication ; DNA-Binding Proteins/genetics/metabolism/*physiology ; Fluorescent Antibody Technique ; Gene Silencing ; Humans ; Kinetochores/metabolism ; Mitosis ; Origin Recognition Complex ; Phenotype ; Polyploidy ; RNA, Small Interfering ; RNA, Untranslated/metabolism/pharmacology ; Recombinant Fusion Proteins/analysis ; Saccharomyces cerevisiae Proteins ; Spindle Apparatus/ultrastructure ; Transfection ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2009-02-07
    Description: Centrosomes, each containing a pair of centrioles, organize microtubules in animal cells, particularly during mitosis. DNA and centrosomes are normally duplicated once before cell division to maintain optimal genome integrity. We report a new role for the Orc1 protein, a subunit of the origin recognition complex (ORC) that is a key component of the DNA replication licensing machinery, in controlling centriole and centrosome copy number in human cells, independent of its role in DNA replication. Cyclin A promotes Orc1 localization to centrosomes where Orc1 prevents Cyclin E-dependent reduplication of both centrioles and centrosomes in a single cell division cycle. The data suggest that Orc1 is a regulator of centriole and centrosome reduplication as well as the initiation of DNA replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653626/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653626/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hemerly, Adriana S -- Prasanth, Supriya G -- Siddiqui, Khalid -- Stillman, Bruce -- CA13106/CA/NCI NIH HHS/ -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-310025/CA/NCI NIH HHS/ -- P01 CA013106-36/CA/NCI NIH HHS/ -- P01 CA013106-370025/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Feb 6;323(5915):789-93. doi: 10.1126/science.1166745.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor 11724, NY, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19197067" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle ; Cell Line, Tumor ; Centrioles/*physiology ; Centrosome/*physiology ; Cyclin A/metabolism ; Cyclin E/metabolism ; Cyclin-Dependent Kinase 2/metabolism ; DNA Replication ; HeLa Cells ; Humans ; Kinetics ; Mutant Proteins/metabolism ; Origin Recognition Complex/genetics/*metabolism ; RNA Interference ; RNA, Small Interfering ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2010-08-05
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
    Publication Date: 2015-07-08
    Description: Ribosome biogenesis dictates the translational capacity of cells. Several mechanisms establish and maintain transcriptional output from eukaryotic ribosomal DNA (rDNA) loci. rDNA silencing is one such mechanism that ensures the inactivity and hence the maintenance of a silenced state of a subset of rRNA gene copies. Whereas oncogenic agents stimulate...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2011-08-10
    Description: Determining the growth patterns of single cells offers answers to some of the most elusive questions in contemporary cell biology: how cell growth is regulated and how cell size distributions are maintained. For example, a linear growth in time implies that there is no regulation required to maintain homeostasis; an exponential pattern indicates the opposite. Recently, there has been great effort to measure single cells using microelectromechanical systems technology, and several important questions have been explored. However, a unified, easy-to-use methodology to measure the growth rate of individual adherent cells of various sizes has been lacking. Here we demonstrate that a newly developed optical interferometric technique, known as spatial light interference microscopy, can measure the cell dry mass of many individual adherent cells in various conditions, over spatial scales from micrometers to millimeters, temporal scales ranging from seconds to days, and cell types ranging from bacteria to mammalian cells. We found evidence of exponential growth in Escherichia coli, which agrees very well with other recent reports. Perhaps most importantly, combining spatial light interference microscopy with fluorescence imaging provides a unique method for studying cell cycle-dependent growth. Thus, by using a fluorescent reporter for the S phase, we measured single cell growth over each phase of the cell cycle in human osteosarcoma U2OS cells and found that the G2 phase exhibits the highest growth rate, which is mass-dependent and can be approximated by an exponential.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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