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Seminar: 'Distinct features of nucleolar proteins contribute to driving forces for assembly and ribosomal RNA flux' (Lecture)

Friday 6 May 2022Add to my calendar
from 14:00
HG00.062 & online
Dr. Matthew King (Washington University, St Louis, USA)

Ribosome biogenesis is the primary process limiting cell growth across all kingdoms of life. This occurs in the nucleolus, which has three discrete phases with specific compositions and functions. This organization is predicted to enable the assembly-line process of ribosomal biogenesis. First, the core of the nucleolus is host to an uncharacterized phase positioned around ribosomal DNA (rDNA) loci termed the fibrillar center (FC). Next, ribosomal RNA (rRNA) is transcribed, spliced, and partially folded in the subsequent phase – the dense fibrillar component (DFC). Finally, in the outermost phase (termed the granular component or GC), rRNA matures and incorporates ribosomal proteins to create ribosomal subunits. Previous work has established that GC-specific scaffolds enable a thermodynamic hand-off of mature rRNA to ribosomal proteins in the final step of ribosome biogenesis. However, our understanding of rRNA flux in two innermost phases (the FC and DFC), as well as their constituent scaffolds, remains almost entirely unknown.

We have determined the key scaffolds and functional organization of the FC and DFC using bioinformatics, in vitro reconstitutions, and in vivo characterizations. The disordered regions within these scaffolds feature a novel molecular grammar consisting of blocks of positively charged Lysine residues and acidic residues. Interestingly, several of these scaffolds have a negative net charge per residue yet exhibit complex coacervation with DNA or RNA, which we experimentally and computationally rationalize. We go on to demonstrate that linked phase and binding equilibria ensure the assembly-line-like organization of FC-DFC and directly facilitate the thermodynamic flux of rRNA. Overall, our investigations have uncovered the core scaffolds of the FC and DFC, established their necessity and sufficiency, and elucidated compelling features of their biophysical nature. We anticipate this work will pave the way for quantitative and predictive insights into nucleolar organization and function, as well as an understanding of complex coacervation of these and related biomolecules.

Amy Yewdall (Spruijt lab)

For zoom link see the invitation mail sent on April 26, 2022