Publications
2017
Valasek L S, Zeman J, Wagner S, Beznoskova P, Pavlíkova Z, Mohammad M P, Hronova V, Herrmannova A, Hashem Y, Gunisova S
Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle Journal Article
In: Nucleic Acids Res, vol. 45, no. 19, pp. 10948-10968, 2017, ISBN: 28981723.
Abstract | Links | BibTeX | Tags: HASHEM, Unité ARN
@article{,
title = {Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle},
author = {L S Valasek and J Zeman and S Wagner and P Beznoskova and Z Pavlíkova and M P Mohammad and V Hronova and A Herrmannova and Y Hashem and S Gunisova},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28981723?dopt=Abstract},
doi = {10.1093/nar/gkx805},
isbn = {28981723},
year = {2017},
date = {2017-01-01},
journal = {Nucleic Acids Res},
volume = {45},
number = {19},
pages = {10948-10968},
abstract = {Protein synthesis is mediated via numerous molecules including the ribosome, mRNA, tRNAs, as well as translation initiation, elongation and release factors. Some of these factors play several roles throughout the entire process to ensure proper assembly of the preinitiation complex on the right mRNA, accurate selection of the initiation codon, errorless production of the encoded polypeptide and its proper termination. Perhaps, the most intriguing of these multitasking factors is the eukaryotic initiation factor eIF3. Recent evidence strongly suggests that this factor, which coordinates the progress of most of the initiation steps, does not come off the initiation complex upon subunit joining, but instead it remains bound to 80S ribosomes and gradually falls off during the first few elongation cycles to: (1) promote resumption of scanning on the same mRNA molecule for reinitiation downstream-in case of translation of upstream ORFs short enough to preserve eIF3 bound; or (2) come back during termination on long ORFs to fine tune its fidelity or, if signaled, promote programmed stop codon readthrough. Here, we unite recent structural views of the eIF3-40S complex and discus all known eIF3 roles to provide a broad picture of the eIF3's impact on translational control in eukaryotic cells.},
keywords = {HASHEM, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2016
Chikne V, Doniger T, Rajan K S, Bartok O, Eliaz D, Cohen-Chalamish S, Tschudi C, Unger R, Hashem Y, Kadener S, Michaeli S
A pseudouridylation switch in rRNA is implicated in ribosome function during the life cycle of Trypanosoma brucei. Journal Article
In: Sci Rep, vol. 6, pp. 25296, 2016, ISBN: 27142987.
Abstract | Links | BibTeX | Tags: HASHEM, Unité ARN
@article{,
title = {A pseudouridylation switch in rRNA is implicated in ribosome function during the life cycle of Trypanosoma brucei.},
author = {V Chikne and T Doniger and K S Rajan and O Bartok and D Eliaz and S Cohen-Chalamish and C Tschudi and R Unger and Y Hashem and S Kadener and S Michaeli},
url = {http://www.ncbi.nlm.nih.gov/pubmed/27142987?dopt=Abstract},
doi = {10.1038/srep25296},
isbn = {27142987},
year = {2016},
date = {2016-01-01},
journal = {Sci Rep},
volume = {6},
pages = {25296},
abstract = {The protozoan parasite Trypanosoma brucei, which causes devastating diseases in humans and animals in sub-Saharan Africa, undergoes a complex life cycle between the mammalian host and the blood-feeding tsetse fly vector. However, little is known about how the parasite performs most molecular functions in such different environments. Here, we provide evidence for the intriguing possibility that pseudouridylation of rRNA plays an important role in the capacity of the parasite to transit between the insect midgut and the mammalian bloodstream. Briefly, we mapped pseudouridines (Ψ) on rRNA by Ψ-seq in procyclic form (PCF) and bloodstream form (BSF) trypanosomes. We detected 68 Ψs on rRNA, which are guided by H/ACA small nucleolar RNAs (snoRNA). The small RNome of both life cycle stages was determined by HiSeq and 83 H/ACAs were identified. We observed an elevation of 21 Ψs modifications in BSF as a result of increased levels of the guiding snoRNAs. Overexpression of snoRNAs guiding modification on H69 provided a slight growth advantage to PCF parasites at 30 °C. Interestingly, these modifications are predicted to significantly alter the secondary structure of the large subunit (LSU) rRNA suggesting that hypermodified positions may contribute to the adaption of ribosome function during cycling between the two hosts.},
keywords = {HASHEM, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2015
Sun M, Li W, Blomqvist K, Das S, Hashem Y, Dvorin J D, Frank J
Dynamical features of the Plasmodium falciparum ribosome during translation. Journal Article
In: Nucleic Acids Res, vol. 43, no. 21, pp. 10515-10524, 2015, ISBN: 26432834.
Abstract | Links | BibTeX | Tags: HASHEM, Unité ARN
@article{,
title = {Dynamical features of the Plasmodium falciparum ribosome during translation.},
author = {M Sun and W Li and K Blomqvist and S Das and Y Hashem and J D Dvorin and J Frank},
url = {http://www.ncbi.nlm.nih.gov/pubmed/26432834?dopt=Abstract},
doi = {10.1093/nar/gkv991},
isbn = {26432834},
year = {2015},
date = {2015-01-01},
journal = {Nucleic Acids Res},
volume = {43},
number = {21},
pages = {10515-10524},
abstract = {Plasmodium falciparum, the mosquito-transmitted Apicomplexan parasite, causes the most severe form of human malaria. In the asexual blood-stage, the parasite resides within erythrocytes where it proliferates, multiplies and finally spreads to new erythrocytes. Development of drugs targeting the ribosome, the site of protein synthesis, requires specific knowledge of its structure and work cycle, and, critically, the ways they differ from those in the human host. Here, we present five cryo-electron microscopy (cryo-EM) reconstructions of ribosomes purified from P. falciparum blood-stage schizonts at sub-nanometer resolution. Atomic models were built from these density maps by flexible fitting. Significantly, our study has taken advantage of new capabilities of cryo-EM, in visualizing several structures co-existing in the sample at once, at a resolution sufficient for building atomic models. We have discovered structural and dynamic features that differentiate the ribosomes of P. falciparum from those of mammalian system. Prompted by the absence of RACK1 on the ribosome in our and an earlier study we confirmed that RACK1 does not specifically co-purify with the 80S fraction in schizonts. More extensive studies, using cryo-EM methodology, of translation in the parasite will provide structural knowledge that may lead to development of novel anti-malarials.},
keywords = {HASHEM, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Liao H Y, Hashem Y, Frank J
Efficient Estimation of Three-Dimensional Covariance and its Application in the Analysis of Heterogeneous Samples in Cryo-Electron Microscopy. Journal Article
In: Structure, vol. 23, no. 6, pp. 1129-1137, 2015, ISBN: 25982529.
Abstract | Links | BibTeX | Tags: HASHEM, Unité ARN
@article{,
title = {Efficient Estimation of Three-Dimensional Covariance and its Application in the Analysis of Heterogeneous Samples in Cryo-Electron Microscopy.},
author = {H Y Liao and Y Hashem and J Frank},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25982529?dopt=Abstract},
doi = {10.1016/j.str.2015.04.004},
isbn = {25982529},
year = {2015},
date = {2015-01-01},
journal = {Structure},
volume = {23},
number = {6},
pages = {1129-1137},
abstract = {Single-particle cryogenic electron microscopy (cryo-EM) is a powerful tool for the study of macromolecular structures at high resolution. Classification allows multiple structural states to be extracted and reconstructed from the same sample. One classification approach is via the covariance matrix, which captures the correlation between every pair of voxels. Earlier approaches employ computing-intensive resampling and estimate only the eigenvectors of the matrix, which are then used in a separate fast classification step. We propose an iterative scheme to explicitly estimate the covariance matrix in its entirety. In our approach, the flexibility in choosing the solution domain allows us to examine a part of the molecule in greater detail. Three-dimensional covariance maps obtained in this way from experimental data (cryo-EM images of the eukaryotic pre-initiation complex) prove to be in excellent agreement with conclusions derived by using traditional approaches, revealing in addition the interdependencies of ligand bindings and structural changes.},
keywords = {HASHEM, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
des Georges A, Dhote V, Kuhn L, Hellen C U, Pestova T V, Frank J, Hashem Y
Structure of mammalian eIF3 in the context of the 43S preinitiation complex. Journal Article
In: Nature, vol. 525, no. 7570, pp. 491-495, 2015, ISBN: 26344199.
Abstract | Links | BibTeX | Tags: HASHEM, PPSE, Unité ARN
@article{,
title = {Structure of mammalian eIF3 in the context of the 43S preinitiation complex.},
author = {A des Georges and V Dhote and L Kuhn and C U Hellen and T V Pestova and J Frank and Y Hashem},
url = {http://www.ncbi.nlm.nih.gov/pubmed/26344199},
doi = {10.1038/nature14891},
isbn = {26344199},
year = {2015},
date = {2015-01-01},
journal = {Nature},
volume = {525},
number = {7570},
pages = {491-495},
abstract = {During eukaryotic translation initiation, 43S complexes, comprising a 40S ribosomal subunit, initiator transfer RNA and initiation factors (eIF) 2, 3, 1 and 1A, attach to the 5'-terminal region of messenger RNA and scan along it to the initiation codon. Scanning on structured mRNAs also requires the DExH-box protein DHX29. Mammalian eIF3 contains 13 subunits and participates in nearly all steps of translation initiation. Eight subunits having PCI (proteasome, COP9 signalosome, eIF3) or MPN (Mpr1, Pad1, amino-terminal) domains constitute the structural core of eIF3, to which five peripheral subunits are flexibly linked. Here we present a cryo-electron microscopy structure of eIF3 in the context of the DHX29-bound 43S complex, showing the PCI/MPN core at ∼6 Å resolution. It reveals the organization of the individual subunits and their interactions with components of the 43S complex. We were able to build near-complete polyalanine-level models of the eIF3 PCI/MPN core and of two peripheral subunits. The implications for understanding mRNA ribosomal attachment and scanning are discussed.},
keywords = {HASHEM, PPSE, Unité ARN},
pubstate = {published},
tppubtype = {article}
}