Abstract : The polymerase of negative-stranded RNA viruses consists of the large protein (L) and the phosphoprotein (P), the latter serving both as a chaperon and a cofactor for L. We mapped within measles virus (MeV) P the regions responsible for binding and stabilizing L and showed that the coiled-coil multimerization domain (MD) of P is required for gene expression. MeV MD is kinked as a result of the presence of a stammer. Both restoration of the heptad regularity and displacement of the stammer strongly decrease or abrogate activity in a minigenome assay. By contrast, P activity is rather tolerant of substitutions within the stammer. Single substitutions at the "a" or "d" hydrophobic anchor positions with residues of variable hydrophobicity revealed that P functionality requires a narrow range of cohesiveness of its MD. Results collectively indicate that, beyond merely ensuring P oligomerization, the MD finely tunes viral gene expression through its cohesiveness.
Louis-Marie Bloyet, Antoine Schramm, Carine Lazert, Bertrand Raynal, Maggy Hologne, et al.. Regulation of measles virus gene expression by P protein coiled-coil properties. Science Advances , American Association for the Advancement of Science (AAAS), 2019, 5 (5), pp.eaaw3702. ⟨10.1126/sciadv.aaw3702⟩. ⟨hal-02133726⟩
