Structural basis for messenger RNA movement on the ribosome

Nature ◽  
2006 ◽  
Vol 444 (7117) ◽  
pp. 391-394 ◽  
Author(s):  
Gulnara Yusupova ◽  
Lasse Jenner ◽  
Bernard Rees ◽  
Dino Moras ◽  
Marat Yusupov
Keyword(s):  
Messenger Rna ◽  
Structural Basis

scholarly journals Structural basis for IFN antagonism by human respiratory syncytial virus nonstructural protein 2

2021 ◽  
Vol 118 (10) ◽  
pp. e2020587118
Author(s):  
Jingjing Pei ◽  
Nicole D. Wagner ◽  
Angela J. Zou ◽  
Srirupa Chatterjee ◽  
Dominika Borek ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Nonstructural Protein ◽  
Human Respiratory Syncytial Virus ◽  
Host Responses ◽  
Structural Basis ◽  
Downstream Signaling ◽  
Nonstructural Protein 2 ◽  
Syncytial Virus

Human respiratory syncytial virus (RSV) nonstructural protein 2 (NS2) inhibits host interferon (IFN) responses stimulated by RSV infection by targeting early steps in the IFN-signaling pathway. But the molecular mechanisms related to how NS2 regulates these processes remain incompletely understood. To address this gap, here we solved the X-ray crystal structure of NS2. This structure revealed a unique fold that is distinct from other known viral IFN antagonists, including RSV NS1. We also show that NS2 directly interacts with an inactive conformation of the RIG-I–like receptors (RLRs) RIG-I and MDA5. NS2 binding prevents RLR ubiquitination, a process critical for prolonged activation of downstream signaling. Structural analysis, including by hydrogen-deuterium exchange coupled to mass spectrometry, revealed that the N terminus of NS2 is essential for binding to the RIG-I caspase activation and recruitment domains. N-terminal mutations significantly diminish RIG-I interactions and result in increased IFNβ messenger RNA levels. Collectively, our studies uncover a previously unappreciated regulatory mechanism by which NS2 further modulates host responses and define an approach for targeting host responses.

scholarly journals Structural basis for functional mimicry of long-variable-arm tRNA by transfer-messenger RNA

2007 ◽  
Vol 104 (20) ◽  
pp. 8293-8298 ◽  
Author(s):  
Y. Bessho ◽  
R. Shibata ◽  
S.-i. Sekine ◽  
K. Murayama ◽  
K. Higashijima ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Structural Basis

scholarly journals Structural basis of mitochondrial translation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Shintaro Aibara ◽  
Vivek Singh ◽  
Angelika Modelska ◽  
Alexey Amunts
Keyword(s):  
Conformational Changes ◽  
Messenger Rna ◽  
Large Subunit ◽  
Small Subunit ◽  
Specific Protein ◽  
Structural Basis ◽  
Mitochondrial Translation ◽  
Dynamic Interactions ◽  
Sequential Mechanism ◽  
Specific Proteins

Translation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the binding of mt-mRNA and to what extent they are involved in the translocation of transfer RNA (mt-tRNA) is unclear. To visualize the process of translation in human mitochondria, we report ~3.0 Å resolution structure of the human mitoribosome, including the L7/L12 stalk, and eight structures of its functional complexes with mt-mRNA, mt-tRNAs, recycling factor and additional trans factors. The study reveals a transacting protein module LRPPRC-SLIRP that delivers mt-mRNA to the mitoribosomal small subunit through a dedicated platform formed by the mitochondria-specific protein mS39. Mitoribosomal proteins of the large subunit mL40, mL48, and mL64 coordinate translocation of mt-tRNA. The comparison between those structures shows dynamic interactions between the mitoribosome and its ligands, suggesting a sequential mechanism of conformational changes.

Mechanism of spliceosome remodeling by the ATPase/helicase Prp2 and its coactivator Spp2

Science ◽  
2020 ◽  
Vol 371 (6525) ◽  
pp. eabe8863
Author(s):  
Rui Bai ◽  
Ruixue Wan ◽  
Chuangye Yan ◽  
Qi Jia ◽  
Jianlin Lei ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Adenosine Triphosphatase ◽  
Biochemical Analysis ◽  
Mrna Splicing ◽  
Structural Basis ◽  
Atomic Structures

Spliceosome remodeling, executed by conserved adenosine triphosphatase (ATPase)/helicases including Prp2, enables precursor messenger RNA (pre-mRNA) splicing. However, the structural basis for the function of the ATPase/helicases remains poorly understood. Here, we report atomic structures of Prp2 in isolation, Prp2 complexed with its coactivator Spp2, and Prp2-loaded activated spliceosome and the results of structure-guided biochemical analysis. Prp2 weakly associates with the spliceosome and cannot function without Spp2, which stably associates with Prp2 and anchors on the spliceosome, thus tethering Prp2 to the activated spliceosome and allowing Prp2 to function. Pre-mRNA is loaded into a featured channel between the N and C halves of Prp2, where Leu536 from the N half and Arg844 from the C half prevent backward sliding of pre-mRNA toward its 5′-end. Adenosine 5′-triphosphate binding and hydrolysis trigger interdomain movement in Prp2, which drives unidirectional stepwise translocation of pre-mRNA toward its 3′-end. These conserved mechanisms explain the coupling of spliceosome remodeling to pre-mRNA splicing.

scholarly journals Structural basis for messenger RNA movement on the ribosome

2007 ◽  
Vol 63 (a1) ◽  
pp. s16-s16
Author(s):  
L. Jenner ◽  
G. Yusupova ◽  
B. Rees ◽  
M. Yusupov
Keyword(s):  
Messenger Rna ◽  
Structural Basis

scholarly journals Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2

Science ◽  
2020 ◽  
Vol 369 (6508) ◽  
pp. 1249-1255 ◽  
Author(s):  
Matthias Thoms ◽  
Robert Buschauer ◽  
Michael Ameismeier ◽  
Lennart Koepke ◽  
Timo Denk ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Nonstructural Protein ◽  
Ribosomal Subunit ◽  
Mrna Translation ◽  
Structural Basis ◽  
Innate Immune Responses ◽  
Structure Based Drug Design ◽  
Nonstructural Protein 1 ◽  
C Terminus

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1), which suppresses host gene expression by ribosome association. Here, we show that Nsp1 from SARS-CoV-2 binds to the 40S ribosomal subunit, resulting in shutdown of messenger RNA (mRNA) translation both in vitro and in cells. Structural analysis by cryo–electron microscopy of in vitro–reconstituted Nsp1-40S and various native Nsp1-40S and -80S complexes revealed that the Nsp1 C terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks retinoic acid–inducible gene I–dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2.

Structural basis for the regulation of splicing of a yeast messenger RNA

Cell ◽  
1991 ◽  
Vol 65 (5) ◽  
pp. 797-804 ◽  
Author(s):  
Francis J. Eng ◽  
Jonathan R. Warner
Keyword(s):  
Messenger Rna ◽  
Structural Basis

scholarly journals Structural basis for the transition from translation initiation to elongation by an 80S-eIF5B complex

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jinfan Wang ◽  
Jing Wang ◽  
Byung-Sik Shin ◽  
Joo-Ran Kim ◽  
Thomas E. Dever ◽  
...  
Keyword(s):  
Single Molecule ◽  
Translation Initiation ◽  
Messenger Rna ◽  
Ribosomal Subunit ◽  
Mrna Translation ◽  
Start Codon ◽  
Structural Basis ◽  
Large Ribosomal Subunit ◽  
Reading Frame ◽  
Fluorescence Measurements

Abstract Recognition of a start codon by the initiator aminoacyl-tRNA determines the reading frame of messenger RNA (mRNA) translation by the ribosome. In eukaryotes, the GTPase eIF5B collaborates in the correct positioning of the initiator Met-tRNAiMet on the ribosome in the later stages of translation initiation, gating entrance into elongation. Leveraging the long residence time of eIF5B on the ribosome recently identified by single-molecule fluorescence measurements, we determine the cryoEM structure of the naturally long-lived ribosome complex with eIF5B and Met-tRNAiMet immediately before transition into elongation. The structure uncovers an unexpected, eukaryotic specific and dynamic fidelity checkpoint implemented by eIF5B in concert with components of the large ribosomal subunit.

scholarly journals Structural basis of transcription-translation coupling

Science ◽  
2020 ◽  
Vol 369 (6509) ◽  
pp. 1359-1365 ◽  
Author(s):  
Chengyuan Wang ◽  
Vadim Molodtsov ◽  
Emre Firlar ◽  
Jason T. Kaelber ◽  
Gregor Blaha ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Escherichia Coli ◽  
Transcription Factors ◽  
Rna Polymerase ◽  
Active Center ◽  
Messenger Rna ◽  
Coupled Processes ◽  
Structural Basis ◽  
Cryo Electron Microscopy ◽  
Translation Coupling

In bacteria, transcription and translation are coupled processes in which the movement of RNA polymerase (RNAP)–synthesizing messenger RNA (mRNA) is coordinated with the movement of the first ribosome-translating mRNA. Coupling is modulated by the transcription factors NusG (which is thought to bridge RNAP and the ribosome) and NusA. Here, we report cryo–electron microscopy structures of Escherichia coli transcription-translation complexes (TTCs) containing different-length mRNA spacers between RNAP and the ribosome active-center P site. Structures of TTCs containing short spacers show a state incompatible with NusG bridging and NusA binding (TTC-A, previously termed “expressome”). Structures of TTCs containing longer spacers reveal a new state compatible with NusG bridging and NusA binding (TTC-B) and reveal how NusG bridges and NusA binds. We propose that TTC-B mediates NusG- and NusA-dependent transcription-translation coupling.

Organization of tight junctions in the choroid plexus epithelium

1978 ◽  
Vol 36 (2) ◽  
pp. 336-337
Author(s):  
B. Van Deurs ◽  
J. K. Koehler
Keyword(s):  
Choroid Plexus ◽  
Present Report ◽  
Freeze Fracture ◽  
Barrier Properties ◽  
Cell Junctions ◽  
Structural Basis ◽  
Apical Surface ◽  
Choroid Plexus Epithelium ◽  
Solid Nitrogen ◽  
Special Composition

The choroid plexus epithelium constitutes a blood-cerebrospinal fluid (CSF) barrier, and is involved in regulation of the special composition of the CSF. The epithelium is provided with an ouabain-sensitive Na/K-pump located at the apical surface, actively pumping ions into the CSF. The choroid plexus epithelium has been described as “leaky” with a low transepithelial resistance, and a passive transepithelial flux following a paracellular route (intercellular spaces and cell junctions) also takes place. The present report describes the structural basis for these “barrier” properties of the choroid plexus epithelium as revealed by freeze fracture.Choroid plexus from the lateral, third and fourth ventricles of rats were used. The tissue was fixed in glutaraldehyde and stored in 30% glycerol. Freezing was performed either in liquid nitrogen-cooled Freon 22, or directly in a mixture of liquid and solid nitrogen prepared in a special vacuum chamber. The latter method was always used, and considered necessary, when preparations of complementary (double) replicas were made.

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