title: 7SK small nuclear RNA directly affects HMGA1 function in transcription regulation.
abstract: Non-coding (nc) RNAs are increasingly recognized to play important regulatory roles in eukaryotic gene expression. The highly abundant and essential 7SK ncRNA has been shown to negatively regulate RNA Polymerase II transcription by inactivating the positive transcription elongation factor b (P-TEFb) in cellular and Tat-dependent HIV transcription. Here, we identify a more general, P-TEFb-independent role of 7SK RNA in directly affecting the function of the architectural transcription factor and chromatin regulator HMGA1. An important regulatory role of 7SK RNA in HMGA1-dependent cell differentiation and proliferation regulation is uncovered with the identification of over 1500 7SK-responsive HMGA1 target genes. Elevated HMGA1 expression is observed in nearly every type of cancer making the use of a 7SK substructure in the inhibition of HMGA1 activity, as pioneered here, potentially useful in therapy. The 7SK-HMGA1 interaction not only adds an essential facet to the comprehension of transcriptional plasticity at the coupling of initiation and elongation, but also might provide a molecular link between HIV reprogramming of cellular gene expression-associated oncogenesis.
authors.affiliation: Institut des Hautes Études Scientifiques & Centre National de la Recherche Scientifique USR3078, 35 route de Chartres, 91440 Bures sur Yvette, France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Eilebrecht
authors.forename: Guillaume
authors.initials: G
authors.lastname: Brysbaert
authors.forename: Thomas
authors.initials: T
authors.lastname: Wegert
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.forename: Bernd-Joachim
authors.initials: BJ
authors.lastname: Benecke
authors.forename: Arndt
authors.initials: A
authors.lastname: Benecke
mesh_terms: D024761:AT-Hook Motifs; D001483:Base Sequence; D001665:Binding Sites; D003164:Competitive Bidding; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D025741:HMGA1a Protein / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D012342:RNA, Small Nuclear / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D012342:RNA, Small Nuclear; D025741:HMGA1a Protein; D004247:DNA