Co-transcriptional rRNA modification HydraPsiSeq. The dual life of nucleolar intrinsically disordered lysine-rich domains: from rRNA modification to nucleolar compaction

Intrinsically disordered regions (IDRs) are highly enriched in the nucleolar proteome. Despite numerous in vitro studies their physiological role in ribosome assembly remains poorly understood and highly debated. Our study sheds light on the function of the most abundant nucleolar lysine-rich IDR in Saccharomyces cerevisiae, the KKE/D domain, which is exclusively present in RNAPI, snoRNPs and RNA helicases. We demonstrate that in exponentially growing yeast cells, KKE/D domains promote the targeting of associated factors in contact with nascent rRNAs to facilitate nucleotide modification, whereas under stress, this IDR is essential for nucleolar compaction and sequestration of a specific set of factors through the ability of KKE/D domains to self-interact. We propose that the dual, growth-dependent role of KKE/D domains constitutes a conserved regulatory system specific to eukaryotes explaining how cells continuously adjust nucleolar morphology and RNAPI activity in a manner dependent on the fluctuating pool of latent snoRNPs, i.e. those not associated with rRNA.