title: MYB elongation is regulated by the nucleic acid binding of NFκB p50 to the intronic stem-loop region.
abstract: MYB transcriptional elongation is regulated by an attenuator sequence within intron 1 that has been proposed to encode a RNA stem loop (SLR) followed by a polyU tract. We report that NFκBp50 can bind the SLR polyU RNA and promote MYB transcriptional elongation together with NFκBp65. We identified a conserved lysine-rich motif within the Rel homology domain (RHD) of NFκBp50, mutation of which abrogated the interaction of NFκBp50 with the SLR polyU and impaired NFκBp50 mediated MYB elongation. We observed that the TAR RNA-binding region of Tat is homologous to the NFκBp50 RHD lysine-rich motif, a finding consistent with HIV Tat acting as an effector of MYB transcriptional elongation in an SLR dependent manner. Furthermore, we identify the DNA binding activity of NFκBp50 as a key component required for the SLR polyU mediated regulation of MYB. Collectively these results suggest that the MYB SLR polyU provides a platform for proteins to regulate MYB and reveals novel nucleic acid binding properties of NFκBp50 required for MYB regulation.
authors: Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, Locked Bag #1, Melbourne, Victoria, 8006, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors: Lloyd A
authors: LA
authors: Pereira
authors: Victorian Breast Cancer Consortium, Invasion and Metastasis Unit, St Vincent's Institute of Medical Research, Melbourne, Victoria, 3065, Australia.
authors: Honor J
authors: HJ
authors: Hugo
authors: Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, Locked Bag #1, Melbourne, Victoria, 8006, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors: Jordane
authors: J
authors: Malaterre
authors: Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, Locked Bag #1, Melbourne, Victoria, 8006, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3010, Australia; The Department of Pathology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors: Xu
authors: X
authors: Huiling
authors: The Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors: Secondo
authors: S
authors: Sonza
authors: Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, Locked Bag #1, Melbourne, Victoria, 8006, Australia.
authors: Alina
authors: A
authors: Cures
authors: The Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors: Damian F J
authors: DF
authors: Purcell
authors: Centre for Immunology, Burnet Institute, Melbourne, Victoria, 3004, Australia; Department of Surgery (Austin Health), The University of Melbourne, Heidelberg, Victoria, 3084, Australia; Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, 3004, Australia.
authors: Paul A
authors: PA
authors: Ramsland
authors: Australian Centre for Blood Diseases, Monash University, Prahran, Victoria 3004, Australia.
authors: Steven
authors: S
authors: Gerondakis
authors: School of Pharmacy University of Queensland, Woolloongabba, Queensland, 4102, Australia.
authors: Thomas J
authors: TJ
authors: Gonda
authors: Differentiation and Transcription Laboratory, Peter MacCallum Cancer Centre, Locked Bag #1, Melbourne, Victoria, 8006, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, 3010, Australia; The Department of Pathology, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors: Robert G
authors: RG
authors: Ramsay
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020570:Genes, myb / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007438:Introns / Q000235:genetics; D055029:Inverted Repeat Sequences / Q000235:genetics; D009154:Mutation; D052002:NF-kappa B p50 Subunit / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D052002:NF-kappa B p50 Subunit; D012367:RNA, Viral