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8 results on '"Boutoual, Rachid"'

3. Human Elp3/Kat9 is a mitochondrial tRNA modifying enzyme

Author

Boutoual, Rachid, primary, Jo, Hyunsun, additional, Heckenbach, Indra, additional, Tiwari, Ritesh, additional, Kasler, Herbert, additional, Lerner, Chad A., additional, Shah, Samah, additional, Schilling, Birgit, additional, Calvanese, Vincenzo, additional, Rardin, Matthew J., additional, Scheibye-Knudsen, Morten, additional, and Verdin, Eric, additional

Published
2022
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4. The MELAS mutation m.3243A>G alters the expression of mitochondrial tRNA fragments

Author

Ministerio de Economía y Competitividad (España), Meseguer, Salvador, Navarro-González, Carmen, Panadero, Joaquín, Villarroya, Magda, Boutoual, Rachid, Sánchez-Alcázar, José Antonio, Armengod, M.-Eugenia, Ministerio de Economía y Competitividad (España), Meseguer, Salvador, Navarro-González, Carmen, Panadero, Joaquín, Villarroya, Magda, Boutoual, Rachid, Sánchez-Alcázar, José Antonio, and Armengod, M.-Eugenia

Abstract

Recent evidences highlight the importance of mitochondria-nucleus communication for the clinical phenotype of oxidative phosphorylation (OXPHOS) diseases. However, the participation of small non-coding RNAs (sncRNAs) in this communication has been poorly explored. We asked whether OXPHOS dysfunction alters the production of a new class of sncRNAs, mitochondrial tRNA fragments (mt tRFs), and, if so, whether mt tRFs play a physiological role and their accumulation is controlled by the action of mt tRNA modification enzymes. To address these questions, we used a cybrid model of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), an OXPHOS disease mostly caused by mutation m.3243A>G in the mitochondrial tRNALeu(UUR) gene. High-throughput analysis of small-RNA-Seq data indicated that m.3243A>G significantly changed the expression pattern of mt tRFs. A functional analysis of potential mt tRFs targets (performed under the assumption that these tRFs act as miRNAs) indicated an association with processes that involve the most common affected tissues in MELAS. We present evidences that mt tRFs may be biologically relevant, as one of them (mt i-tRF GluUUC), likely produced by the action of the nuclease Dicer and whose levels are Ago2 dependent, down-regulates the expression of mitochondrial pyruvate carrier 1 (MPC1), promoting the build-up of extracellular lactate. Therefore, our study underpins the idea that retrograde signaling from mitochondria is also mediated by mt tRFs. Finally, we show that accumulation of mt i-tRF GluUUC depends on the modification status of mt tRNAs, which is regulated by the action of stress-responsive miRNAs on mt tRNA modification enzymes.

Published
2019

8. The African striped mouse Lemniscomys barbarus as a model for aggression. Brain areas activated by agonistic encounters

Author

El Mlili, Nisrin, Boutoual, Rachid, Sanchez-Perez, Ana M., Ouarour, Ali, Chakir, Ibtissam, Errami, Mohammed, and Olucha-Bordonau, Francisco E.

Subjects
Emotion, Aggression, C-fos, Immediate early genes, Social behavior, Fear, Amygdala
Abstract

During agonistic behavior several brain areas became differentially activated depending on the role the subject is taking. Several areas are mostly activated during the offender role and several others are activated if the subject plays a defensive role. The main goal of this work is to study in detail the anatomic areas involved in agonistic behavior using a novel animal model, the striped mouse Lemniscomys barbarus, a North African diurnal rodent well known by its natural high aggressiveness toward conspecifics. After social encounters, neural activation in brain areas related to agonistic behavior was measured by c-fos immunostaining. The encounters were recorded and behaviors related to the encounter were analyzed. We differentiated between the aggressive behavior (offender) and escape behavior (defender or defeated). Our results showed that conspecific confrontation induced general c-fos activation in both offender and defender in all measured areas in comparison with non-confronted control. Differences in neural activity between offender and defender were observed specifically in the lateral, cortical and medial amygdala, suprachiasmatic nucleus and the nucleus incertus, suggesting a potential role of these areas in displaying different kinds of behavior during conspecific confrontation. We found that, while in the lateral, medial and cortical amygdala defenders express significantly more c-fos than offenders, in the nucleus incertus of the brainstem the differential activation is just the opposite, Additionally, defenders display significantly more freezing than offenders. This work provides data showing that Lemniscomys barbarus is a widely useful model to study the anatomic background supporting agonistic behavior. This research was supported by the following grants: 51 0935-Tempus-1-2010, TEMPUS IV EU (RB), Generalitat Valenciana AICO/2015/042; Universitat Jaume I P1·1A2014-06 (AMS).

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