Diffusion-mediated HEI10 coarsening can explain meiotic crossover positioning in Arabidopsis

AbstractIn most organisms, the number and distribution of crossovers that occur during meiosis are tightly controlled. All chromosomes must receive at least one ‘obligatory crossover’ and crossovers are prevented from occurring near one another by ‘crossover interference’. However, the mechanistic basis of this phenomenon of crossover interference has remained mostly mysterious. Using quantitative super-resolution cytogenetics and mathematical modelling, we investigate crossover positioning in the Arabidopsis thaliana wild-type, an over-expressor of the conserved E3 ligase HEI10, and a hei10 heterozygous line. We show that crossover positions can be explained by a predictive, diffusion-mediated coarsening model, in which large, approximately evenly-spaced HEI10 foci grow at the expense of smaller, closely-spaced clusters. We propose this coarsening process explains many aspects of Arabidopsis crossover positioning, including crossover interference. Consistent with this model, we also demonstrate that crossover positioning can be predictably modified in vivo simply by altering HEI10 dosage, with higher and lower dosage leading to weaker and stronger crossover interference, respectively. As HEI10 is a conserved member of the RING finger protein family that functions in the interference-sensitive pathway for crossover formation, we anticipate that similar mechanisms may regulate crossover positioning in diverse eukaryotes.

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Ring Finger Protein 213 Assembles into a Sensor for ISGylated Proteins with Antimicrobial Activity

10.1101/2021.06.03.446796 ◽

2021 ◽

Author(s):

Fabien Thery ◽

Lia Martina ◽

Caroline Asselman ◽

Heidi Repo ◽

Yifeng Zhang ◽

...

Keyword(s):

Antimicrobial Activity ◽

Ring Finger ◽

Ring Finger Protein ◽

Microbial Infection ◽

Herpes Simplex Virus 1 ◽

Finger Protein ◽

Syncytial Virus ◽

Simplex Virus

ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we used a viral-like particle trapping technology to identify ISG15-binding proteins and discovered Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly-characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We found that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We showed that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection with Listeria monocytogenes, herpes simplex virus 1 (HSV-1), human respiratory syncytial virus (RSV) and coxsackievirus B3 (CVB3), and we observed a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide novel molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector.

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The Peripubertal Decline in Makorin Ring Finger Protein 3 Expression is Independent of Leptin Action

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa059 ◽

2020 ◽

Vol 4 (7) ◽

Author(s):

Stephanie A Roberts ◽

Ana Paula Abreu ◽

Victor M Navarro ◽

Joy N Liang ◽

Caroline A Maguire ◽

...

Keyword(s):

Arcuate Nucleus ◽

Pubertal Development ◽

Ring Finger ◽

Central Precocious Puberty ◽

Mrna Levels ◽

Ring Finger Protein ◽

Loss Of Function ◽

Wild Type ◽

Finger Protein ◽

Significant Difference

Abstract A critical body weight is necessary for pubertal development, an effect mediated in part by leptin. The potential regulation by leptin of Makorin Ring Finger Protein 3 (MKRN3), in which loss-of-function mutations are the most common genetic cause of central precocious puberty, has not been previously explored. In mice, expression of Mkrn3 in the hypothalamic arcuate nucleus is high early in life and declines before the onset of puberty. Therefore, we aimed to explore if leptin contributes to the decrease in hypothalamic Mkrn3 mRNA levels observed in mice during pubertal development. We first used a leptin-deficient (ob/ob) mouse model. Mkrn3 mRNA levels in the mediobasal hypothalamus (MBH), which includes the arcuate nucleus, and in the preoptic area (POA), both showed a significant decrease with age from postnatal day (PND) 12 to PND30 in ob/ob mice in both males and females, similar to that observed in wild-type mice. To further explore the effects of leptin on Mkrn3 expression, we exposed prepubertal wild-type mice to high levels of leptin from age PND9-12, which did not result in any significant difference in Mkrn3 expression levels in either the MBH or POA. In summary, regulation of Mkrn3 expression by leptin was not observed in either the MBH or the POA, 2 hypothalamic sites important for pubertal maturation. These data suggest that the decline in Mkrn3 at the onset of puberty may occur independently of leptin and support our hypothesis that MKRN3 is a bona fide controller of puberty initiation.

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RING finger protein 10 attenuates vascular restenosis by inhibiting vascular smooth muscle cell hyperproliferation in vivo and vitro

IUBMB Life ◽

10.1002/iub.1995 ◽

2018 ◽

Vol 71 (5) ◽

pp. 632-642 ◽

Cited By ~ 2

Author(s):

Siyu Li ◽

Guiquan Yu ◽

Fuyu Jing ◽

Hui Chen ◽

Aoyi Liu ◽

...

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Vascular Smooth Muscle Cell ◽

Ring Finger ◽

Ring Finger Protein ◽

Finger Protein ◽

Vascular Restenosis

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Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity

Nature Communications ◽

10.1038/s41467-021-26061-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Fabien Thery ◽

Lia Martina ◽

Caroline Asselman ◽

Yifeng Zhang ◽

Madeleine Vessely ◽

...

Keyword(s):

Antimicrobial Activity ◽

Ring Finger ◽

Ring Finger Protein ◽

Microbial Infection ◽

Herpes Simplex Virus 1 ◽

Finger Protein ◽

Syncytial Virus ◽

Simplex Virus

AbstractISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we use a virus-like particle trapping technology to identify ISG15-binding proteins and discover Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We report that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We show that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection with Listeria monocytogenes, herpes simplex virus 1, human respiratory syncytial virus and coxsackievirus B3, and we observe a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector.

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RNF5, a RING Finger Protein That Regulates Cell Motility by Targeting Paxillin Ubiquitination and Altered Localization

Molecular and Cellular Biology ◽

10.1128/mcb.23.15.5331-5345.2003 ◽

2003 ◽

Vol 23 (15) ◽

pp. 5331-5345 ◽

Cited By ~ 66

Author(s):

Christine Didier ◽

Limor Broday ◽

Anindita Bhoumik ◽

Sharon Israeli ◽

Shoichi Takahashi ◽

...

Keyword(s):

Cell Motility ◽

Ring Finger ◽

Focal Adhesions ◽

Normal Growth ◽

Ring Finger Protein ◽

C Elegans ◽

Amino Terminal ◽

Finger Protein

ABSTRACT RNF5 is a RING finger protein found to be important in the growth and development of Caenorhabditis elegans. The search for RNF5-associated proteins via a yeast two-hybrid screen identified a LIM-containing protein in C. elegans which shows homology with human paxillin. Here we demonstrate that the human homologue of RNF5 associates with the amino-terminal domain of paxillin, resulting in its ubiquitination. RNF5 requires intact RING and C-terminal domains to mediate paxillin ubiquitination. Whereas RNF5 mediates efficient ubiquitination of paxillin in vivo, protein extracts were required for in vitro ubiquitination, suggesting that additional modifications and/or an associated E3 ligase assist RNF5 targeting of paxillin ubiquitination. Mutant Ubc13 efficiently inhibits RNF5 ubiquitination, suggesting that RNF5 generates polychain ubiquitin of the K63 topology. Expression of RNF5 increases the cytoplasmic distribution of paxillin while decreasing its localization within focal adhesions, where it is primarily seen under normal growth. Concomitantly, RNF5 expression results in inhibition of cell motility. Via targeting of paxillin ubiquitination, which alters its localization, RNF5 emerges as a novel regulator of cell motility.

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