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  • 1
    Language: English
    In: The Biochemical journal, 10 May 2017, Vol.474(11), pp.1755-1768
    Description: The RUNX1 transcription factor is a critical regulator of normal haematopoiesis and its functional disruption by point mutations, deletions or translocations is a major causative factor leading to leukaemia. In the majority of cases, genetic changes in RUNX1 are linked to loss of function classifying it broadly as a tumour suppressor. Despite this, several recent studies have reported the need for a certain level of active RUNX1 for the maintenance and propagation of acute myeloid leukaemia and acute lymphoblastic leukaemia cells, suggesting an oncosupportive role of RUNX1. Furthermore, in solid cancers, RUNX1 is overexpressed compared with normal tissue, and RUNX factors have recently been discovered to promote growth of skin, oral, breast and ovarian tumour cells, amongst others. RUNX factors have key roles in stem cell fate regulation during homeostasis and regeneration of many tissues. Cancer cells appear to have corrupted these stem cell-associated functions of RUNX factors to promote oncogenesis. Here, we discuss current knowledge on the role of RUNX genes in stem cells and as oncosupportive factors in haematological malignancies and epithelial cancers.
    Keywords: Cbfβ ; Runx ; Cancer ; Leukaemia ; Stem Cells ; Models, Molecular ; Core Binding Factor Alpha 2 Subunit -- Metabolism ; Neoplasm Proteins -- Metabolism ; Neoplasms -- Metabolism ; Stem Cells -- Metabolism
    ISSN: 02646021
    E-ISSN: 1470-8728
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  • 2
    In: Nature, 2011, Vol.471(7340), p.602
    Description: CRISPR/Cas systems constitute a widespread class of immunity systems that protect bacteria and archaea against phages and plasmids, and commonly use repeat/spacer-derived short crRNAs to silence foreign nucleic acids in a sequence-specific manner. Although the maturation of crRNAs represents a key event in CRISPR activation, the responsible endoribonucleases (CasE, Cas6, Csy4) are missing in many CRISPR/Cas subtypes. Here, differential RNA sequencing of the human pathogen Streptococcus pyogenes uncovered tracrRNA, a trans -encoded small RNA with 24 nucleotide complementarity to the repeat regions of crRNA precursor transcripts. We show that tracrRNA directs the maturation of crRNAs by the activities of the widely conserved endogenous RNase III and the CRISPR-associated Csn1 protein; all these components are essential to protect S. pyogenes against prophage-derived DNA. Our study reveals a novel pathway of small guide RNA maturation and the first example of a host factor (RNase III) required for bacterial RNA-mediated immunity against invaders.
    Keywords: Article;
    ISSN: 0028-0836
    E-ISSN: 14764687
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