7SK RNA, a non-coding RNA regulating P-TEFb, a general transcription factor

Abstract

Human 7SK RNA is an abundant 331nt nuclear transcript generated by RNA polymerase III. Binding of 7SK RNA to HEXIM1/2 turns these proteins into inhibitors of P-TEFb (Positive transcriptional elongation factor b). P-TEFb is required for RNA polymerase II transcription elongation. 7SK RNA is released from P-TEFb/HEXIM/7SK complexes upon an arrest in transcription and physiological stimulations such as cardiac hypertrophy, leading to P-TEFb activation. The released 7SK RNA associates a subset of heterogeneous nuclear ribonucleoproteins (hnRNP). 7SK RNA has been evolutionary conserved in vertebrates and homologues are found in annelid, mollusc and insect genomes. 7SK RNA folds into several hairpins that serve as specific platforms for binding proteins. It is stabilized by mono-methylation of its 5’-triphosphate group and binding of a specific La-Related protein, LARP7 at its 3’ end. As the likely best characterized example, 7SK RNA is a paradigm for non-coding RNAs regulating transcription.