Biology subjects

Niu, F.

Publications and source records attributed to Niu, F..

6 recordsLinked to original sources

bioRxiv2026

Coordinated phase separation and phase transition underlie synaptic ribbon condensate formation and plasticity

Mesoscale molecular apparatuses with diverse functions are widespread in cells. How mesoscale cellular apparatuses are formed and regulated is poorly understood. The synaptic ribbon in sensory neurons, which can dynamically adjust its size and shape in response to light or sound, is a mesoscale molecular assembly. In this study, we demonstrate that RIBEYE, the backbone protein of synaptic ribbons, via combined ordered and disordered interactions, forms micron-sized dynamic molecular assemblies. Integrated cryo-electron microscopy and tomography studies revealed that the N-terminal SAM domain and the C-terminal B domain of RIBEYE form distinct nanoscale filaments and further assemble into ribbon-like architectures via phase transition. Unexpectedly, the N-terminal intrinsically disordered region of RIBEYE softens the solid mesoscale ribbon structures via phase separation. The mesoscale size and shape of the RIBEYE condensate are bidirectionally tuned by physiological modulators such as Piccolino and CtBP1, linking synaptic ribbon structural plasticity to functional adaptability. Thus, our study demonstrates that combined phase transition and phase separation of nanoscale protein oligomers can build mesoscale functional cellular apparatuses.

biochemistry↗

bioRxiv2024

Oligomerization of PRMT1 Regulated RNA-Binding Protein Cascade Promotes Pancreatic Ductal Adenocarcinoma

PRMT1 is the predominant type I protein arginine methyltransferase responsible for generating monomethylarginine and asymmetric dimethylarginine (MMA and ADMA) in various protein substrates. It regulates numerous biological processes, including RNA metabolism, mRNA splicing, DNA damage repair, and chromatin dynamics. The crystal structure of rat PRMT1 has been previously reported as a homodimer; however, higher-order oligomeric species of human PRMT1 have been observed in vivo, and their structural basis remains elusive. In this study, we present the cryo-EM structure of human PRMT1 in its oligomeric form, revealing novel interfaces crucial for PRMT1 self-assembly and normal function. PRMT1 shows a strong preference for intrinsically disordered RGG/RG motifs, which are commonly found in RNA-binding proteins (RBPs), highlighting its critical role in regulating RNA metabolism. In vitro studies indicate that disrupting PRMT1 oligomerization impairs its binding affinity for RGG motif substrates, thereby reducing arginine methylation levels on these substrates. This finding emphasizes the essential role of the oligomeric state of PRMT1 in its function with RGG motif-containing RBPs. In vivo, the loss of PRMT1 oligomerization leads to decreased global ADMA levels in pancreatic ductal adenocarcinoma (PDAC) cells and inhibits PDAC tumor growth. Collectively, we propose that PRMT1 oligomerization, rather than mere dimerization, is sufficient for PRMT1-driven PDAC tumor growth, offering novel insights into the potential therapeutic targeting of PRMT1 oligomeric forms in PDAC. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/627716v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1ed6232org.highwire.dtl.DTLVardef@1c9e688org.highwire.dtl.DTLVardef@3e2c43org.highwire.dtl.DTLVardef@1cbf33e_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2023

Ythdf2 ablation protects aged retina from RGC dendrite shrinking and visual decline

Aging-related retinal degeneration and vision loss have been severely affecting the elder worldwide. Previously we showed that the m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells (RGC) in mice (Niu et al. 2022). Here, we show that conditional ablation of Ythdf2 protects retina from RGC dendrite shrinking and vision loss in the aged mice. Further, we identify Hspa12a and Islr2 as the YTHDF2 target mRNAs mediating these effects. Together our results indicate that m6A modification regulates retinal degeneration caused by aging, which might provide therapeutical potentials for developing new treatment approaches against aging-related vision loss.

neuroscience↗

bioRxiv2021

The m6A reader YTHDF2 is a negative regulator for dendrite development and maintenance of retinal ganglion cells

The precise control of growth and maintenance of the retinal ganglion cell (RGC) dendrite arborization is critical for normal visual functions in mammals. However, the underlying mechanisms remain elusive. Here we find that the m6A reader YTHDF2 is highly expressed in the mouse RGCs. Conditional knockout (cKO) of Ythdf2 in the retina leads to increased RGC dendrite branching, resulting in more synapses in the inner plexiform layer. Interestingly, the Ythdf2 cKO mice show improved visual acuity compared with control mice. We further demonstrate that Ythdf2 cKO in the retina protects RGCs from dendrite degeneration caused by the experimental acute glaucoma model. We identify the m6A-modified YTHDF2 target transcripts which mediate these effects. This study reveals mechanisms by which YTHDF2 restricts RGC dendrite development and maintenance. YTHDF2 and its target mRNAs might be valuable in developing new treatment approaches for glaucomatous eyes. Impact statementThe m6A reader YTHDF2 negatively regulates RGC dendrite branching through destabilizing its m6A-modified target mRNAs encoding proteins controlling dendrite development and maintenance. Ythdf2 cKO improves visual acuity and alleviates acute ocular hypertension-induced glaucoma in mice.

neuroscience↗

bioRxiv2019

The Abnormal Oswald Ripening of Protein Nanofiber in Myofibrillar Protein Solution

In solutions of myofibrillar protein extracted from giant squid (Dosidicus gigas), the size-coarsening process of protein nanofiber is complex. At high temperature (25{degrees}C), nanofiber keeps growth but with two distinguishable patterns, slow rate at the initial stage with t0.2 and the fast one at the late stage with t2.3. The intersection of these two slopes is around 300 min. Meanwhile, protein concentration in solution enhances as well. These behaviors contradict to the prediction of Ostwald ripening. Thus, we call this process as abnormal. These abnormal behaviors come from the conformation change of some types of constitution protein molecules with chemical potential reduction when they dissolve from nanofiber to solution. On the other hand, low temperature (10{degrees}C) depresses this size growth. This observation suggests that temperature regulates protein molecule conformation change in nanofiber. The consequence of this abnormal Ostwald ripening process is that all protein molecules in nanofiber are redistributed. Protein molecules with the absence of conformation change in dissolution accumulate in nanofiber to cause it growing, while the rest concentrates in solution.

biophysics↗

bioRxiv2017

In vivo Imaging β-cell Function Reveals Two Waves of β-cell Maturation

The insulin-secreting cells generated from stem cells in vitro are less glucose responsive than primary {beta}-cells. To search for the missing ingredients that are needed for {beta}-cell maturation, we have longitudinally monitored function of every {beta}-cell in Tg (ins:Rcamp1.07) zebrafish embryos with a newly-invented two-photon light-sheet microscope. We have shown that {beta}-cell maturation begins from the islet mantle and propagates to the islet core during the hatching period, coordinated by the islet vascularization. Lower concentration of glucose is optimal to initiate {beta}-cell maturation, while increased glucose delivery to every cell through microcirculation is required for functional boosting of the {beta}-cells. Both the initiation and the boosting of {beta}-cell maturation demands activation of calcineurin/NFAT by glucose. Calcineurin activator combined with glucose promotes mouse neonatal {beta}-cells cultured in vitro to mature to a functional state similar to adult {beta}-cells, suggesting a new strategy for improving stem cell-derived {beta}-like cell function in vitro.

developmental biology↗