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Hala Ahmad Chamieh

Associate professor
Life & Earth Sciences department - Section III - Tripoli
Speciality: Biology
Specific Speciality: Biologie

Positions
2006 - 2008 : Research Scientist

Center of molecular genetics
Paris- France

Teaching 9 Taught Courses
(2014-2015) BIOA 426 - Bioinformatics

M1 Cellular and Molecular Biology - Section 3

(2014-2015) BIOA 427 - Bioinformatics Lab

M1 Cellular and Molecular Biology - Section 3

(2014-2015) BIOA 427 - Bioinformatics Lab

M1 Cellular and Molecular Biology - Section 3

(2014-2015) Biol 111 - Organisation of the living world animal, Reproduction, and Embryology

BS Earth and life sciences

(2014-2015) BIOA 421 - Project

M1 Cellular and Molecular Biology - Section 3

(2014-2015) BIOC 400 - Molecular Biology II

M1 Cellular and Molecular Biology - Section 3

(2014-2015) BIOV 425 - General Biotechnology Lab

M1 Cellular and Molecular Biology - Section 3

(2014-2015) BIOV 425 - General Biotechnology Lab

M1 Cellular and Molecular Biology - Section 3

(2014-2015) Biol 381 - Microbiology and Molecular Genetics Lab

BS Biochemistry

Publications 5 publications
Chamieh H, Marty V, Guetta D, Perollier A, Franzetti B Stress regulation of the PAN-proteasome system in the extreme halophilic archaeon Halobacterium Extremophiles 2012

In Archaea, the importance of the proteasome system for basic biological processes is only poorly understood. Proteasomes were partially purified from Halobacterium by native gradient density ultracentrifugation. The peptidase activity profiles showed that the 20S proteasome accumulation is altered depending on the physiological state of the cells. The amount of active 20S particles increases in Halobacterium cells as a response to thermal and low salt stresses. In the same conditions, Northern experiments showed a positive transcriptional regulation of the alpha and beta proteasome subunits as well as of the two proteasome regulatory ATPases, PANA and PANB. Co-immunoprecipitation experiments demonstrated the existence of a physical interaction between the two Proteasome Activating Nucleotidase (PAN) proteins in cell extracts. Thus, a direct regulation occurs on the PAN-proteasome components to adjust the protein degradation activity to growth and environmental constraints. These results also indicate that, in extreme halophiles, proteasome mediated proteolysis is an important aspect of low salt stress response. The tri-peptide vinyl sulfone inhibitor NLVS was used in cell cultures to study the in vivo function of proteasome in Halobacterium. The chemical inhibition of proteasomes was measured in the cellular extracts. It has no effect on cell growth and mortality under normal growth conditions as well as under heat shock conditions. These results suggest that the PAN activators or other proteases compensate for loss of proteasome activity in stress conditions

Chamieh H, Guetta D, Franzetti B. The two PAN ATPases from Halobacterium display N-terminal heterogeneity and form labile complexes with the 20S proteasome. Biochemical Journal 2008

The PAN (proteasome-activating nucleotidase) proteins from archaea represent homologues of the eukaryotic 26S proteasome regulatory ATPases. In vitro the PAN complex has been previously shown to have a stimulatory effect on the peptidase activities of the 20S core. By using gradient ultracentrifugation we found that, in cellular extracts, the two PAN proteins from Halobacterium do not form stable high-molecular-mass complexes. Only PAN B was found to associate transiently with the 20S proteasome, thus suggesting that the two PAN proteins are not functionally redundant. The PAN B-20S proteasome complexes associate in an ATP-dependent manner and are stabilized upon nucleotide binding. The two PAN proteins were immunodetected in cellular extracts as N-terminal-truncated polypeptides. RNA-mapping experiments and sequence analysis indicated that this process involved transcript heterogeneities and dual translational initiation mechanisms. Taken together, our results suggest that PAN N-terminal modifications and their intracellular dynamics of assembly/association may constitute important determinants of proteolysis regulation.

Nielsen KH, Chamieh H, Andersen CB, Fredslund F, Hamborg K, Le Hir H, Andersen GR Mechanism of ATP turnover inhibition in the EJC. RNA 2008

Search term Clear input Advanced Help Result Filters Abstract Send to: RNA. 2009 Jan;15(1):67-75. doi: 10.1261/rna.1283109. Epub 2008 Nov 25. Mechanism of ATP turnover inhibition in the EJC. Nielsen KH1, Chamieh H, Andersen CB, Fredslund F, Hamborg K, Le Hir H, Andersen GR. Author information Abstract The exon junction complex (EJC) is deposited onto spliced mRNAs and is involved in many aspects of mRNA function. We have recently reconstituted and solved the crystal structure of the EJC core made of MAGOH, Y14, the most conserved portion of MLN51, and the DEAD-box ATPase eIF4AIII bound to RNA in the presence of an ATP analog. The heterodimer MAGOH/Y14 inhibits ATP turnover by eIF4AIII, thereby trapping the EJC core onto RNA, but the exact mechanism behind this remains unclear. Here, we present the crystal structure of the EJC core bound to ADP-AIF(3), the first structure of a DEAD-box helicase in the transition-mimicking state during ATP hydrolysis. It reveals a dissociative transition state geometry and suggests that the locking of the EJC onto the RNA by MAGOH/Y14 is not caused by preventing ATP hydrolysis. We further show that ATP can be hydrolyzed inside the EJC, demonstrating that MAGOH/Y14 acts by locking the conformation of the EJC, so that the release of inorganic phosphate, ADP, and RNA is prevented. Unifying features of ATP hydrolysis are revealed by comparison of our structure with the EJC-ADPNP structure and other helicases. The reconstitution of a transition state mimicking complex is not limited to the EJC and eIF4AIII as we were also able to reconstitute the complex Dbp5-RNA-ADP-AlF(3), suggesting that the use of ADP-AlF(3) may be a valuable tool for examining DEAD-box ATPases in general.

Chamieh H1, Ballut L, Bonneau F, Le Hir H NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity Nature Structural Molecular Biology 2008

Nonsense-mediated mRNA decay (NMD) eliminates mRNAs containing a premature translation termination codon through the recruitment of the conserved NMD factors UPF1, UPF2 and UPF3. In humans, a dynamic assembly pathway allows UPF1 to join UPF2 and UPF3 recruited to the mRNA by the exon-junction complex (EJC). Here we show that the recombinant EJC core is sufficient to reconstitute, with the three UPF proteins, a stable heptameric complex on RNA. The EJC proteins MAGOH, Y14 and eIF4AIII provide a composite binding site for UPF3b that serves as a bridge to UPF2 and UPF1. In the UPF trimeric complex, UPF2 and UPF3b cooperatively stimulate both ATPase and RNA helicase activities of UPF1. This work demonstrates that the EJC core is sufficient to stably anchor the UPF proteins to mRNA and provides insights into the regulation of its central effector, UPF1.

Andersen CB, Ballut L, Johansen JS, Chamieh H, Nielsen KH, Oliveira CL, Pedersen JS, Séraphin B, Le Hir H, Andersen GR. Structure of the exon Junction complex with a trap DEAD-box ATPase bound to RNA Science 2006

In higher eukaryotes, a multiprotein exon junction complex is deposited on spliced messenger RNAs. The complex is organized around a stable core, which serves as a binding platform for numerous factors that influence messenger RNA function. Here, we present the crystal structure of a tetrameric exon junction core complex containing the DEAD-box adenosine triphosphatase (ATPase) eukaryotic initiation factor 4AIII (eIF4AIII) bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic. eIF4AIII interacts with the phosphate-ribose backbone of six consecutive nucleotides and prevents part of the bound RNA from being double stranded. The MAGOH and Y14 subunits lock eIF4AIII in a prehydrolysis state, and activation of the ATPase probably requires only modest conformational changes in eIF4AIII motif I.

Languages
Arabic

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English

Full professional proficiency

French

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