MYB elongation is regulated by the nucleic acid binding of NFκB p50 to the intronic stem-loop region

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...

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Bibliographic Details
Published in:PloS one 2015-04, Vol.10 (4), p.e0122919-e0122919
Main Authors: Pereira, Lloyd A, Hugo, Honor J, Malaterre, Jordane, Huiling, Xu, Sonza, Secondo, Cures, Alina, Purcell, Damian F J, Ramsland, Paul A, Gerondakis, Steven, Gonda, Thomas J, Ramsay, Robert G
Format: Article
Language:English
Subjects:
Acids
Binding
Breast cancer
Colorectal cancer
Deoxyribonucleic acid
DNA
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Elongation
Gene expression
Genes, myb - genetics
HIV-1 - genetics
HIV-1 - pathogenicity
Homology
Humans
Immunology
Introns - genetics
Inverted Repeat Sequences - genetics
Kinases
Laboratories
Lysine
Medical research
Mutation
NF-kappa B p50 Subunit - genetics
NF-kappa B p50 Subunit - metabolism
NF-κB protein
Nucleic acids
Nucleotide sequence
Oncology
Pathology
Proteins
Ribonucleic acid
RNA
RNA, Viral - genetics
Tat protein
Transcription elongation
Transcription factors
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0122919