Alexandra Henrion-Caude

French Institute of Health and Medical Research | Inserm · Unit of Genetics and Epigenetics of Neurometabolic Diseases and Birth Defects

Since the start of the COVID-19 outbreak, the race for testing new platforms designed to confer immunity against SARS-CoV-2, has been rampant and unprecedented, leading to conditional emergency authorization of various vaccines. Despite progress on early multidrug therapy for COVID-19 patients, the current mandate is to immunize the world populatio...

Since the start of the COVID-19 outbreak, the race for testing new platforms designed to confer immunity against SARS-CoV-2, has been rampant and unprecedented, leading to conditional emergency authorization of various vaccines. Despite progress on early multidrug therapy for COVID-19 patients, the current mandate is to immunize the world populatio...

(1) Background: Previous experimental observations and theoretical hypotheses have been providing insight into a hypothetical world where an RNA hairpin or ring may have debuted as the primary informational and functional molecule. We propose a model revisiting the architecture of RNA-peptide interactions at the origin of life through the evolution...

A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish emb...

Background and aim: To improve the diagnostic work-up of patients with diverse neurological diseases, we have elaborated specific clinical and CSF neurotransmitter patterns. Methods: Neurotransmitter determinations in CSF from 1200 patients revealed abnormal values in 228 (19%) cases. In 54/228 (24%) patients, a final diagnosis was identified....

Mitochondria play a pivotal role in cellular energy-generating processes and are considered master regulators of cell life and death fate. Mitochondrial function integrates signalling networks in several metabolic pathways controlling neurogenesis and neuroplasticity. Indeed, dysfunctional mitochondria and mitochondrial-dependent activation of intr...

Over the course of his distinguished career, Morinet’s biggest gift to the community was his humanity and his sense of transmission.

Neonatal sclerosing cholangitis (NSC) is a rare biliary disease leading to liver transplantation in childhood. Patients with NSC and ichtyosis have been already identified with a CLDN1 mutation, encoding a tight-junction protein. However, for the majority of patients the molecular basis of NSC remains unknown. We identified biallelic missense mutat...

Biliary atresia (BA) is a rare and severe inflammatory and obliterative cholangiopathy that affects both extra- and intrahepatic bile ducts. BA symptoms occur shortly after birth with jaundice, pale stools and dark urines. The prognosis of BA has dramatically changed in the last decades: before the Kasai operation most BA patients died, while nowad...

Genetic regulatory networks are devoted to the control of important functions like cell energy, organ morphogenesis, and animal immune defense. Since the innate system of defense represented by the Toll-like receptors (TLRs, already present in insects), mammals have developed an adaptive immune system during the embryonic maturation of their T-cell...

Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder which is characterized by bone metaphysis anomalies with manifestations that include short stature, defective cellular immunity, and predisposition to several cancers. It is caused by mutations in RMRP, which is transcribed as an RNA component of the mitochondrial RNA-processing rib...

Protein synthesis is a primary energy-consuming process in the cell. Therefore, under hypoxic conditions, rapid inhibition of global mRNA translation represents a major protective strategy to maintain energy metabolism. How some mRNAs, especially those that encode crucial survival factors, continue to be efficiently translated in hypoxia is not com...

##Assembly-Data-START## Sequencing Technology :: Sanger dideoxy sequencing ##Assembly-Data-END##

##Assembly-Data-START## Sequencing Technology :: Sanger dideoxy sequencing ##Assembly-Data-END##

When he came across the human genome the Little Prince, inspired from Saint- Exupery, respectfully saluted the geneticist. "Good morning. Why did you just sequence? - Those are the orders, replied the geneticist. - What are the orders? - The orders are to sequence the genes. And he sequenced the genome of another individual. And a gene,what is a ge...

MicroRNAs have been discovered in the noncoding nuclear genome. They inhibit partly in a nonspecific manner the transcription of numerous genes, and the corresponding “inhibitory noise” prevents the weakest positive interactions of the genetic regulatory networks to be actually efficient, hence microRNAs control the number of attractors of these ne...

Unlabelled: Microvillous inclusion disease (MVID) is a congenital disorder of the enterocyte related to mutations in the MYO5B gene, leading to intractable diarrhea often necessitating intestinal transplantation (ITx). Among our cohort of 28 MVID patients, 8 developed a cholestatic liver disease akin to progressive familial intrahepatic cholestasi...

Over the course of cortical neurogenesis, the transition of progenitors from proliferation to differentiation requires a precise regulation of involved gene networks under varying environmental conditions. In order to identify such regulatory mechanisms, we analyzed microRNA (miRNA) target networks in progenitors during early and late stages of neu...

MicroRNAs are non-coding parts of nuclear and mitochondrial genomes, preventing the weakest part of the genetic regulatory networks from being expressed and preventing the appearance of a too many attractors in these networks. They have also a great influence on the chromatin clock, which ensures the updating of the genetic regulatory networks. The...

Mitochondria play a crucial role in the energetic metabolism, signaling pathways, and overall cell viability. Mitochondrial dysfunctions are known to cause a wide range of human diseases that affect especially tissues with high energetic requirement, such as skeletal muscle, heart, kidney and central nervous system, whilst being involved in cancer,...

Hirschsprung disease (HSCR) genetics is a paradigm for the study and understanding of multigenic disorders. Association between Down syndrome and HSCR suggests that genetic factors that predispose to HSCR map to chromosome 21. To identify these additional factors, we performed a dose-dependent association study on chromosome 21 in Down syndrome pat...

Number of F1 and F2 configurations (F1+F2) and M1 and M2 configurations (M1+M2) when calling genotypes with the K-means method for independent individuals. (DOC)

MicroRNAs are parts of nuclear and mitochondrial genomes which pertain to the not coding genome. They have a partly unspecific role of inhibition, preventing the weakest part of the genetic regulatory networks to be expressed and preventing the appearance of a too large number of attractors in these networks, i.e., forcing the network to have only...

Friedreich's ataxia (FRDA) is a severe neurodegenerative disease caused by GAA repeat expansion within the first intron of the frataxin gene. It has been suggested that the repeat is responsible for the disease severity due to impaired transcription thereby reducing expression of the protein. However, genotype-phenotype correlation is imperfect, an...

Insulin-like growth factors (IGF-I and -II) are pleiotropic regulators of somatic growth and development in vertebrate species. Endocrine and paracrine effects of both hormones are mediated by a common IGF type 1 receptor (IGF-1R). Lethal respiratory failure in neonatal IGF-1R knockout mice suggested a particular role for this receptor in pulmonary...

Introduction: The search for the molecular basis of human disease has focused mainly on coding sequences, although they only account for about 1.9% of the human genome (Encode consortium, 2004). The availability of genome sequences of various species allowed genomic comparison and showed that about 3% of genomes, although noncoding, are under high...

To date, the general assumption was that most mutations interested protein-coding genes only. Thus, only few illustrations have mentioned here that mutations may occur in non-protein coding genes such as microRNAs (miRNAs). We thus report progress in delineating their contribution as phenotypic modulators, genetic switches and fine-tuners of gene e...

We wish to call the readership’s attention to the recent study by Boonstra et al. [1] on the systematic review that showed that the incidence and the prevalence of primary sclerosing cholangitis and primary biliary cirrhosis vary widely based on the geographical distribution. Further, it was previously observed that the severity and the incidence o...

The human genome is densely populated with transposons and transposon-like repetitive elements. Although the impact of these transposons and elements on human genome evolution is recognized, the significance of subtle variations in their sequence remains mostly unexplored. Here we report homozygosity mapping of an infantile neurodegenerative diseas...

Mitochondria as Novel Players of the Cellular RNA Interference • S. Bandiera, • S. Hanein, • S. Lyonnet and • Alexandra Henrion-Caude¹ • Inserm U781 and Imagine Foundation, Department of Genetics, University Paris Descartes, Hospital Necker-Enfants Malades, Paris, France • ↵1E-mail: alexandra.caude{at}inserm.fr Huang et al. (1) recently reporte...

MicroRNAs (miRNAs) are key regulators of gene expression in animals and plants. Studies in a variety of model organisms show that miRNAs modulate developmental processes. To our knowledge, the only hereditary condition known to be caused by a miRNA is a form of adult-onset non-syndromic deafness, and no miRNA mutation has yet been found to be respo...

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The general architecture of a genetic regulatory network consists of strong connected components of its interaction graph, to which are attached three kinds of sub-structures: -a set of up-trees, rooted in the sources of the interaction graph, represented either by small RNAs like microRNAs: nuclear miRs or mitochondrial mitomiRs, i.e., translation...

MiRNA profiling of HeLa mitochondria with or without RNase A treatment. (PDF)

Ontology enrichment analysis for target genes of hsa-miR-328, hsa-miR-494, hsa-miR-513 and hsa-miR-638. (TIFF)

Prediction of subcellular localizations of AGO2. (DOC)

Compilation of target genes and/or genes co-regulated with hsa-miR-328, hsa-mir-494, hsa-mir-513 and hsa-mir-638. (DOC)

Comparison of miRNA expression data in HeLa cells. (TIFF)

Nuclear-encoded computational target genes of mitomiRs and control miRNAs. (DOC)

Mitochondrial enrichment in miRNA targets predicted for mitomiRs and control miRNAs. (DOC)

Number of miRNA target sites on the mitochondrial genome predicted for mitomiRs and control miRNAs. (DOC)

Lengths and thermodynamic features of mitomiRs. (DOC)

Mitochondrial enrichment among predicted miRNA targets of mitomiRs and control miRNAs. (TIFF)

Measurement of enzymatic activities in mitochondrial fraction. (DOC)

Compiled miRNA expression profiling data in HeLa cells. (DOC)

Comparison of MFE, AMFE, MFEI of mitomiRs and control miRNAs. (DOC)

MicroRNAs (miRNAs) are small non-coding RNAs that associate with Argonaute proteins to regulate gene expression at the post-transcriptional level in the cytoplasm. However, recent studies have reported that some miRNAs localize to and function in other cellular compartments. Mitochondria harbour their own genetic system that may be a potential site...

MicroRNAs (miRNAs) are key regulators of gene expression in animals and plants. Studies in a variety of model organisms show that miRNAs modulate developmental processes. To our knowledge, the only hereditary condition known to be caused by a miRNA is a form of adult-onset non-syndromic deafness, and no miRNA mutation has yet been found to be respo...

WNK1 and WNK4 encode two members of the WNK serine-threonine kinase subfamily. Greater WNK1 expression associates with higher BP. A combination of promoters, enhancers, repressors, and insulators regulate WNK1 expression, but whether microRNAs also modulate WNK1 expression is unknown. Here, computational analysis revealed the presence of a target s...

The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET. In a study of 690 European- and 192 Chinese-descent probands and their parents or controls, we demonstrate the ubiquity of a >4-fold susceptibility from a C-->T allele (rs2435357: p = 3.9 x 10(-43) in European ancestry; p = 1.1 x 10(-21) in Chinese samples) tha...

Until recently, the search for genetic factors predisposing or causing Mendelian diseases focused almost exclusively on protein coding sequences. As essential components of the regulatory system of gene expression, microRNAs (miRNAs) hold great promises into elucidating a number of inherited diseases. The herein review focuses on the genetic variat...

The clinical course of cystic fibrosis (CF) varies considerably among patients carrying the same CF-causing gene mutation. Additional genetic modifiers may contribute to this variability. As airway inflammation is a key component of CF pathophysiology, we investigated whether major cytokine variants represent such modifiers in young CF patients. We...

Cystic fibrosis is a lethal inherited disorder caused by mutations in a single gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, resulting in progressive oxidative lung damage. In this study, we evaluated the role of CFTR in the control of ubiquitin-proteasome activity and nuclear factor (NF)-kappaB/IkappaB-alpha...

Recent studies have uncovered profound and unexpected roles for a family of tiny regulatory RNAs, known as microRNAs (miRNAs), in the control of diverse aspects of hepatic function and dysfunction, including hepatocyte growth, stress response, metabolism, viral infection and proliferation, gene expression, and maintenance of hepatic phenotype. In l...

Cystic fibrosis (CF) is a lethal disease caused by defective function of the cftr gene product, the CF transmembrane conductance regulator (CFTR) that leads to oxidative damage and excessive inflammatory response in lungs of CF patients. We here report the effects of oxidative stress (hyperoxia, 95% O(2)) on the expression of pro-inflammatory inter...

The variability in the inflammatory burden of the lung in cystic fibrosis (CF) patients together with the variable effect of glucocorticoid treatment led us to hypothesize that glucocorticoid receptor (GR) gene polymorphisms may affect glucocorticoid sensitivity in CF and, consequently, may contribute to variations in the inflammatory response. We...

Lung epithelium in cystic fibrosis (CF) patients is characterized by structural damage and altered repair due to oxidative stress. To gain insight into the oxidative stress-related damage in CF, we studied the effects of hyperoxia in CF and normal lung epithelial cell lines. In response to a 95% O2 exposure, both cell lines exhibited increased reac...

It is presently unknown whether any member of the IGFBP (insulin-like growth factor binding protein) family directly participates in the control of cell proliferation. We have previously documented that induction of IGFBP-2 was associated with inhibition of DNA synthesis in lung alveolar epithelial cells. In the present study, we investigated the r...

Recent evidence suggests that genetic polymorphisms that affect the production of interleukin (IL)–10 may play a role in the response to pathogens in cystic fibrosis (CF). The present study was designed to investigate a possible association between alleles carried at position −1082 in the promoter region of the IL-10 gene and clinical data on 378 p...

Cellular responses to aging and oxidative stress are regulated by type 1 insulin-like growth factor receptor (IGF-1R). Oxidant injury, which is implicated in the pathophysiology of a number of respiratory diseases, acutely upregulates IGF-1R expression in the lung. This led us to suspect that reduction of IGF-1R levels in lung tissue could prevent...

The pathological changes observed in interstitial lung disease (ILD) are characterised by derangements of the alveolar walls. For a long time, the prevailing hypothesis has emphasised the key role of a persistent alveolitis that injures the lung and modulates fibrogenesis, regardless of initiating agents. The current concept on ILD pathogenesis rel...

Progression and severity of lung disease differs markedly and early between patients with cystic fibrosis (CF). We investigated the hypothesis that polymorphisms in the detoxifying enzymes glutathione-S-transferase (GST) could influence phenotypic presentation of lung disease in CF. Genotypes for GSTM1, GSTM3, GSTP1 and GSTT1 were determined in a c...