Intermolecular recognition of the non-coding RNA 7SK and HEXIM protein in perspective.

A 7SKsnRNP complex, comprising the non-coding RNA 7SK and proteins MePCE and LARP7, participates in the regulation of the transcription elongation by RNA-polymerase II in higher eukaryotes. Binding of a HEXIM protein triggers the inhibition of the kinase complex P-TEFb, a key actor of the switch from paused transcription to elongation. The present paper reviews what is known about the specific recognition of the 7SK RNA by the HEXIM protein. HEXIM uses an arginine-rich motif (ARM) peptide to bind one specific site in the 5'-hairpin of the 7SK RNA. Since HEXIM forms a dimer, what happens with the second ARM impacts the assembly symmetry. In order to help sort through possible models, a combination of native mass spectrometry and electrophoretic mobility shift assays was used. It provides evidence that only one ARM of the HEXIM dimer is directly binding to the RNA hairpin and that another sequence downstream of the ARM participates in a second binding event allowing the other monomer of HEXIM to bind the RNA.