Banani Salman F, Goychuk Andriy, Natarajan Pradeep, Zheng Ming M, Dall'Agnese Giuseppe, Henninger Jonathan E, Kardar Mehran, Young Richard A, Chakraborty Arup K
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
bioRxiv. 2024 Oct 13:2024.10.12.614958. doi: 10.1101/2024.10.12.614958.
Biomolecular condensates are membraneless compartments that organize biochemical processes in cells. In contrast to well-understood mechanisms describing how condensates form and dissolve, the principles underlying condensate patterning - including their size, number and spacing in the cell - remain largely unknown. We hypothesized that RNA, a key regulator of condensate formation and dissolution, influences condensate patterning. Using nucleolar fibrillar centers (FCs) as a model condensate, we found that inhibiting ribosomal RNA synthesis significantly alters the patterning of FCs. Physical theory and experimental observations support a model whereby active RNA synthesis generates a non-equilibrium state that arrests condensate coarsening and thus contributes to condensate patterning. Altering FC condensate patterning by expression of the FC component TCOF1 impairs ribosomal RNA processing, linking condensate patterning to biological function. These results reveal how non-equilibrium states driven by active chemical processes regulate condensate patterning, which is important for cellular biochemistry and function.
生物分子凝聚物是细胞内组织生化过程的无膜区室。与描述凝聚物如何形成和溶解的已充分理解的机制不同，凝聚物图案化背后的原理——包括它们在细胞中的大小、数量和间距——在很大程度上仍然未知。我们推测，作为凝聚物形成和溶解的关键调节因子的RNA会影响凝聚物图案化。使用核仁纤维中心（FCs）作为模型凝聚物，我们发现抑制核糖体RNA合成会显著改变FCs的图案化。物理理论和实验观察支持一种模型，即活跃的RNA合成产生一种非平衡状态，这种状态会阻止凝聚物的粗化，从而有助于凝聚物图案化。通过FC成分TCOF1的表达改变FC凝聚物图案化会损害核糖体RNA加工，将凝聚物图案化与生物学功能联系起来。这些结果揭示了由活跃化学过程驱动的非平衡状态如何调节凝聚物图案化，这对细胞生物化学和功能很重要。
