Chaperonic function of a C/D snoRNA dictates the structure and function of translating ribosomes

Leishmania cause cutaneous and visceral diseases affecting millions worldwide. The parasite cycle between insect and mammalian hosts. In this study, we determined the landscape of 2-O- methylation (Nm) modification on the rRNA and found that two positions change during cycling between its two life stages. Overexpression of LM32Cs1C1 snoRNA guiding one of these positions compromised growth affecting translation. CryoEM structure of ribosomes from cells overexpressing the snoRNA and its mutant version that cannot guide Nm at ~2.4 A resolution, suggested no structural changes in small subunit rRNA carrying the Nm modification but changes were observed in H68 of the large subunit rRNA reflecting the function of a second rRNA interaction domain with the snoRNA. Most surprisingly, a similar structural change was obtained in colon cancer cells overexpressing the homologous snoRD16 highlighting the chaperonic function of snoRNA in dictating ribosome structure and function which is conserved in evolution.