Micropipette aspiration reveals differential RNA-dependent viscoelasticity of nucleolar subcompartments DOI Creative Commons
Holly H. Cheng, James V. Roggeveen, Huan Wang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(22)

Published: May 28, 2025

The nucleolus is a multiphasic biomolecular condensate that facilitates ribosome biogenesis, complex process involving hundreds of proteins and RNAs. proper execution biogenesis likely depends on the material properties nucleolus. However, these remain poorly understood due to challenges in vivo measurements. Here, we use micropipette aspiration (MPA) directly characterize viscoelasticity interfacial tensions nucleoli within transcriptionally active Xenopus laevis oocytes. We examine major nucleolar subphases, outer granular component (GC) inner dense fibrillar (DFC), which itself contains third small phase known as center (FC). show behavior GC more liquid-like, while DFC/FC consistent with partially viscoelastic solid. To determine role ribosomal RNA properties, degrade using RNase A, causes become fluid-like alters tension. Together, our findings suggest underlies solid-like provide insights into how near-native environment are related their RNA-dependent function.

Language: Английский

Increased burden of rare risk variants across gene expression networks predisposes to sporadic Parkinson’s disease DOI Creative Commons

Elena Eubanks,

Katelyn VanderSleen,

Jiya Mody

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(5), P. 115636 - 115636

Published: May 1, 2025

Alpha-synuclein (αSyn) is an intrinsically disordered protein that accumulates in the brains of patients with Parkinson's disease (PD). Through a high-throughput screen, we recently identified 38 genes whose knockdown modulates αSyn propagation. Here, show that, among those, TAX1BP1 regulates how interacts lipids, and ADAMTS19 phase separates into inclusions, adding to growing body evidence implicating those processes PD. RNA sequencing, identify several are differentially expressed after or carry increased frequency rare risk variants PD versus healthy controls. Those cluster within modules regions brain develop high degrees pathology. We propose model for genetic architecture sporadic PD: burden across networks dysregulates pathways underlying homeostasis leads pathology neurodegeneration.

Language: Английский

Citations

0
Micropipette aspiration reveals differential RNA-dependent viscoelasticity of nucleolar subcompartments DOI Creative Commons
Holly H. Cheng, James V. Roggeveen, Huan Wang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(22)

Published: May 28, 2025

The nucleolus is a multiphasic biomolecular condensate that facilitates ribosome biogenesis, complex process involving hundreds of proteins and RNAs. proper execution biogenesis likely depends on the material properties nucleolus. However, these remain poorly understood due to challenges in vivo measurements. Here, we use micropipette aspiration (MPA) directly characterize viscoelasticity interfacial tensions nucleoli within transcriptionally active Xenopus laevis oocytes. We examine major nucleolar subphases, outer granular component (GC) inner dense fibrillar (DFC), which itself contains third small phase known as center (FC). show behavior GC more liquid-like, while DFC/FC consistent with partially viscoelastic solid. To determine role ribosomal RNA properties, degrade using RNase A, causes become fluid-like alters tension. Together, our findings suggest underlies solid-like provide insights into how near-native environment are related their RNA-dependent function.

Language: Английский

Citations

0