Publications & Reports

MYB Elongation Is Regulated by the Nucleic Acid Binding of NFkappaB p50 to the Intronic Stem-Loop Region.

Pereira LA, Hugo HJ, Malaterre J, Huiling X, Sonza S, Cures A, Purcell DF, Ramsland PA, Gerondakis S, Gonda TJ, Ramsay RG
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.

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 NFkappaBp50 can bind the SLR polyU RNA and promote MYB transcriptional elongation together with NFkappaBp65. We identified a conserved lysine-rich motif within the Rel homology domain (RHD) of NFkappaBp50, mutation of which abrogated the interaction of NFkappaBp50 with the SLR polyU and impaired NFkappaBp50 mediated MYB elongation. We observed that the TAR RNA-binding region of Tat is homologous to the NFkappaBp50 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 NFkappaBp50 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 NFkappaBp50 required for MYB regulation.

Publication

  • Journal: PloS One
  • Published: 08/04/2015
  • Volume: 10
  • Issue: 4
  • Pagination: e0122919

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