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Last update 08 May 2025

RMI1

Last update 08 May 2025

Basic Info

Synonyms

BLAP75, BLM-associated protein of 75 kDa, C9orf76

+ [5]

Introduction

Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability.

Drugs associated with RMI1

PIP-199

Target

FANCM x RMI1 x RMI2

Mechanism

FANCM inhibitors [+2]

Active Org.

The University of Sydney

Originator Org.

The University of Sydney

Active Indication

Bloom Syndrome [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with RMI1

100 Translational Medicine associated with RMI1

0 Patents (Medical) associated with RMI1

160

Literatures (Medical) associated with RMI1

22 Apr 2025·Nucleic Acids Research

Deciphering the human TopIIIα activity modulated by Rmi1 using magnetic tweezers

Article

Author: Strick, Terence R ; Yun, Long ; Garnier, Florence ; Nadal, Marc

AbstractTopoisomerases IA (TopoIAs) are universal and essential enzymes present in the three domains of life. Most of the Metazoa exhibit two TopoIAs—TopIIIα and TopIIIβ—assuming different roles in the cell. TopIIIα is essential for genome stability by disentangling precatenanes and hemicatenanes during DNA replication or dissolving the double Holliday junctions in recombination, with the help of several partners, such as Rmi1. However, the detail of the TopIIIα enzymatic cycle and the precise role of Rmi1 remain essentially unknown. The single-molecule approach allows to deconvolute the different early reaction steps and distinguish between intrinsic catalytic characteristics of human TopIIIα that are invariable and those that can be modulated by Rmi1. We determined that the limiting step is the TopIIIα–DNA binding, which requires a small single-stranded region. TopIIIα punctuates its catalytic cycle with long pause times to stabilize the open cleaved complex. Rmi1 helps TopIIIα trap the single-stranded DNA and therefore greatly increases the efficiency of the binding step. Rmi1 also enhances the stabilization of the open cleaved complex to favour intermolecular reactions with improved discrimination of DNA substrates. Rmi1 is therefore a crucial partner for TopIIIα in ensuring that the DNA transaction processes run smoothly in vivo.

01 Dec 2024·The Plant Journal

RMI1 is essential for maintaining rice genome stability at high temperature

Article

Author: Wang, Xiaofeng ; Yu, Hengxiu ; Dai, Qiang ; Zhang, Chao ; Feng, Haiyang ; Liu, Kangwei ; Wang, Lengjing ; Wang, Mengna

SUMMARYHeat is a critical environmental stress for plant survival. One of its harmful effects on the cells is the disruption of genome integrity. However, the mechanisms by which plants cope with heat‐induced DNA damage remain largely unknown. RMI1, a component of the RTR (RECQ4‐TOP3α‐RMI1) complex, plays a pivotal role in maintaining genome stability. In this study, we identified the target gene RMI1 by characterizing a high‐temperature‐sensitive mutant. The growth and development of rmi1‐1 seedlings carrying a non‐frameshift mutation in RMI1 were hindered at 38°C. Abnormal mitotic chromosome behaviours ultimately led to the cell death of root tips. Additionally, the presence of chromosome fragments during anaphase I caused pollen abortion and sterility in rmi1‐1 plants. Yeast two‐hybrid assays revealed that the interactions between RMI1‐1 and RECQ4 or TOP3α were weakened with increasing temperature and entirely ceased at 36°C. In contrast, the functional RMI1 maintained its interactions with RECQ4 or TOP3α under the same conditions. These results indicate that the non‐frameshift mutation in RMI1 disrupts the formation of the RTR complex at high temperatures, leading to defects in DNA repair and increased sensitivity of rmi1‐1 under heat stress. However, embryos of the rmi1‐cr2 mutant with a frameshift mutation in RMI1 exhibited complete lethality. In addition, the overexpression of RMI1 enhanced the heat tolerance in rice. These findings provide insights into the molecular mechanisms that RMI1 responds to high temperatures by maintaining genome stability in rice.

01 Oct 2024·The Lancet Oncology

Risk-prediction models in postmenopausal patients with symptoms of suspected ovarian cancer in the UK (ROCkeTS): a multicentre, prospective diagnostic accuracy study

Article

Author: Keating, Patrick ; Manchanda, Ranjit ; Naskretski, Adam ; Kaushik, Sonali ; Gajjar, Ketankumar ; Selvi-Vikram, Radhika ; Sengupta, Partha ; Ramsay, Bruce ; Blake, Dominic ; Moshy, Roger ; Kwong, Fong Lien ; Timmerman, Dirk ; Sharma, Aarti ; Rosello, Natalia ; Roberts, Mark ; Palmer, Julia ; Hebblethwaite, Neil ; Baron, Sonali ; Hughes, Tracey ; Agarwal, Ridhi ; Menon, Usha ; Exley, Kendra ; Abdelbar, Ahmed ; Rick, Caroline ; Wood, Nicholas ; Scandrett, Katie ; Davenport, Clare ; Ottridge, Ryan ; Sturdy, Lauren ; Balogun, Moji ; Gentry-Maharaj, Alex ; Jermy, Karen ; Stobart, Hilary ; Sayasneh, Ahmad ; Tarang, Majmudar ; Neal, Richard D ; Harmer, Marianne ; Kehoe, Sean ; Gnanachandran, Chellappah ; Ames, Victoria ; Van Calster, Ben ; Russell, Michelle ; Kent, Robert ; Darwish, Ahmed ; Sundar, Sudha ; Abedin, Parveen ; Parker, Rob ; Macdonald, Robert ; Bourne, Tom ; Duncan, Tim ; Abdi, Shahram ; Vita, Lavanya ; Mallett, Sue ; Malhotra, Vivek ; Ciara, Mackenzie ; Nagar, Hans ; Johnson, Susanne ; Rai, Harinder ; Ghazal, Fateh ; Sinha, Anju ; Alawad, Hafez ; Deeks, Jon

BACKGROUNDMultiple risk-prediction models are used in clinical practice to triage patients as being at low risk or high risk of ovarian cancer. In the ROCkeTS study, we aimed to identify the best diagnostic test for ovarian cancer in symptomatic patients, through head-to-head comparisons of risk-prediction models, in a real-world setting. Here, we report the results for the postmenopausal cohort.METHODSIn this multicentre, prospective diagnostic accuracy study, we recruited newly presenting female patients aged 16-90 years with non-specific symptoms and raised CA125 or abnormal ultrasound results (or both) who had been referred via rapid access, elective clinics, or emergency presentations from 23 hospitals in the UK. Patients with normal CA125 and simple ovarian cysts of smaller than 5 cm in diameter, active non-ovarian malignancy, or previous ovarian malignancy, or those who were pregnant or declined a transvaginal scan, were ineligible. In this analysis, only postmenopausal participants were included. Participants completed a symptom questionnaire, gave a blood sample, and had transabdominal and transvaginal ultrasounds performed by International Ovarian Tumour Analysis consortium (IOTA)-certified sonographers. Index tests were Risk of Malignancy 1 (RMI1) at a threshold of 200, Risk of Malignancy Algorithm (ROMA) at multiple thresholds, IOTA Assessment of Different Neoplasias in the Adnexa (ADNEX) at thresholds of 3% and 10%, IOTA SRRisk model at thresholds of 3% and 10%, IOTA Simple Rules (malignant vs benign, or inconclusive), and CA125 at 35 IU/mL. In a post-hoc analysis, the Ovarian Adnexal and Reporting Data System (ORADS) at 10% was derived from IOTA ultrasound variables using established methods since ORADS was described after completion of recruitment. Index tests were conducted by study staff masked to the results of the reference standard. The comparator was RMI1 at the 250 threshold (the current UK National Health Service standard of care). The reference standard was surgical or biopsy tissue histology or cytology within 3 months, or a self-reported diagnosis of ovarian cancer at 12 month follow-up. The primary outcome was diagnostic accuracy at predicting primary invasive ovarian cancer versus benign or normal histology, assessed by analysing the sensitivity, specificity, C-index, area under receiver operating characteristic curve, positive and negative predictive values, and calibration plots in participants with conclusive reference standard results and available index test data. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN17160843).FINDINGSBetween July 13, 2015, and Nov 30, 2018, 1242 postmenopausal patients were recruited, of whom 215 (17%) had primary ovarian cancer. 166 participants had missing, inconclusive, or other reference standard results; therefore, data from a maximum of 1076 participants were used to assess the index tests for the primary outcome. Compared with RMI1 at 250 (sensitivity 82·9% [95% CI 76·7 to 88·0], specificity 87·4% [84·9 to 89·6]), IOTA ADNEX at 10% was more sensitive (difference of -13·9% [-20·2 to -7·6], p<0·0001) but less specific (difference of 28·5% [24·7 to 32·3], p<0·0001). ROMA at 29·9 had similar sensitivity (difference of -3·6% [-9·1 to 1·9], p=0·24) but lower specificity (difference of 5·2% [2·5 to 8·0], p=0·0001). RMI1 at 200 had similar sensitivity (difference of -2·1% [-4·7 to 0·5], p=0·13) but lower specificity (difference of 3·0% [1·7 to 4·3], p<0·0001). IOTA SRRisk model at 10% had similar sensitivity (difference of -4·3% [-11·0 to -2·3], p=0·23) but lower specificity (difference of 16·2% [12·6 to 19·8], p<0·0001). IOTA Simple Rules had similar sensitivity (difference of -1·6% [-9·3 to 6·2], p=0·82) and specificity (difference of -2·2% [-5·1 to 0·6], p=0·14). CA125 at 35 IU/mL had similar sensitivity (difference of -2·1% [-6·6 to 2·3], p=0·42) but higher specificity (difference of 6·7% [4·3 to 9·1], p<0·0001). In a post-hoc analysis, when compared with RMI1 at 250, ORADS achieved similar sensitivity (difference of -2·1%, 95% CI -8·6 to 4·3, p=0·60) and lower specificity (difference of 10·2%, 95% CI 6·8 to 13·6, p<0·0001).INTERPRETATIONIn view of its higher sensitivity than RMI1 at 250, despite some loss in specificity, we recommend that IOTA ADNEX at 10% should be considered as the new standard-of-care diagnostic in ovarian cancer for postmenopausal patients.FUNDINGUK National Institute of Heath Research.

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RMI1

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