Recent investigations have identified homologs of eukaryotic box C/D small nucleolar RNAs (snoRNAs) in Archaea termed sRNAs. Archaeal homologs of the box C/D snoRNP core proteins fibrillarin and Nop56/58 have also been identified but a homolog for the eukaryotic 15.5kD snoRNP protein has not been described. Our sequence analysis of archaeal genomes reveals that the highly conserved ribosomal protein L7 exhibits extensive homology with the eukaryotic 15.5kD protein. Protein binding studies demonstrate that recombinant Methanoccocus jannaschii L7 protein binds the box C/D snoRNA core motif with the same specificity and affinity as the eukaryotic 15.5kD protein. Identical to the eukaryotic 15.5kD core protein, archaeal L7 requires a correctly folded box C/D core motif and intact boxes C and D. Mutational analysis demonstrates that critical features of the box C/D core motif essential for 15.5kD binding are also required for L7 interaction. These include stem I which juxtaposes boxes C and D, as well as the sheared G:A pairs and protruded pyrimidine nucleotide of the asymmetric bulge region. The demonstrated presence of L7Ae in the Haloarcula marismortui 50S ribosomal subunit, taken with our demonstration of the ability of L7 to bind to the box C/D snoRNA core motif, indicates that this protein serves a dual role in Archaea. L7 functioning as both an sRNP core protein and a ribosomal protein could potentially regulate and coordinate sRNP assembly with ribosome biogenesis.

Significance: G-quadruplexes (G4) are 4-stranded nucleic acid secondary structures. MYC is a critical oncogene with a G4 in its promoter (MycG4), which acts as a transcription silencer. MycG4 is very stable and the pathological activation of MYC in cancers requires its active unfolding. We reveal herein that DDX5, a founding member of the DEAD-box RNA helicase family, can unfold DNA G4s. The unfolding mechanism of DDX5 is distinct from previously characterized G4 helicases. Importantly, DDX5 activates MYC gene transcription by proficiently unfolding the promoter MycG4. DDX5 is overexpressed in cancers and the DDX5–MycG4 interaction can be inhibited by small molecules to downregulate MYC . Therefore, our results suggest a new molecular target to suppress MYC for cancer intervention.