Small nucleolar C/D box RNAs (SNORDs) belong to a well-known family of antisense non-coding RNAs that direct sequence-specific 2′-O-methylations on ribosomal RNAs, spliceosomal snRNAs or transfer RNAs. However, the precise mode of action of some of them has not yet been formally demonstrated. In other words, we do not know their RNA targets in vivo. The scientific objectives of our team are to deepen our knowledge of these “orphan SNORDs” and, in so doing, to better understand the function of post-transcriptional RNA modifications. To achieve our goals, we are developing reverse genetic approaches in model organisms (e.g. mouse, zebrafish, fly).
My presentation will be organized into two parts. First, I will summarize our ongoing work on neuron-specific SNORDs whose genes are regulated by genomic imprinting (their expression is restricted to the paternally inherited allele). Specifically, I will discuss the molecular and physiological role of one of them – namely SNORD115 – which represents one of the very few examples showing a regulatory role in modifying mRNAs (i.e. transcripts encoding the serotonin 2C receptor). The possibility that loss of SNORD115 contributes to some aspects of the pathophysiology of Prader-Willi syndrome will also be discussed. Finally, I will briefly mention our unpublished research on SNORD13 and its role in targeting rRNA base modification (i.e. N4-acetyl-cytidine in helix 45 of 18S rRNA).
Published on January 20, 2022