scholarly journals Nonstandard RNA/RNA Interactions Likely Enhance Folding and Stability of Segmented Ribosomes.

RNA ◽  
2021 ◽  
pp. rna.079006.121
Author(s):  
Mario Rivas ◽  
George E Fox
Keyword(s):  
Protein Synthesis ◽  
Hydrogen Bonds ◽  
Trypanosoma Brucei ◽  
Leishmania Donovani ◽  
Ribosome Assembly ◽  
28S Rrna ◽  
Base Pairs ◽  
True Nature ◽  
Overall Stability ◽  
Standard Base

The ribosome is the molecular factory that catalyzes all coded protein synthesis in extant organisms. Eukaryotic ribosomes are typically assembled out of four rRNAs, namely 5S, 5.8S, 18S, and 28S. However, the 28S rRNA of some trypanosomatid organisms has been found to be segmented into six independent rRNAs of different sizes. The two largest segments have multiple sites where they jointly form stems comprised of standard base pairs that can hold them together. However, such regions of interaction are not observed among the four smaller RNAs. Early reports suggested that trypanosomatid segmented ribosome assembly was essentially achieved thanks to their association with rProteins. However, examination of Cryo-EM ribosomal structures from Trypanosoma brucei, Leishmania donovani and Trypanosoma cruzi reveals several long-range nonstandard RNA/RNA interactions. Most of these interactions are clusters of individual hydrogen bonds and so are not readily predictable. However, taken as a whole, they represent significant stabilizing energy that likely facilitates rRNA assembly and the overall stability of the segmented ribosomes. In the context of origin of life studies, the current results provide a better understanding of the true nature of RNA sequence space and what might be possible without an RNA replicase.

The Order of Phase Transition of Solvable DNA Melting Models

2003 ◽  
Vol 17 (16) ◽  
pp. 885-896 ◽  
Author(s):  
Su-Long Nyeo ◽  
I-Ching Yang
Keyword(s):  
Phase Transition ◽  
Hydrogen Bonds ◽  
Short Range ◽  
Scaling Laws ◽  
Dna Melting ◽  
Thermodynamic Quantities ◽  
Base Pairs ◽  
Order Of Phase Transition ◽  
Exactly Solvable ◽  
Dna Models

The phase transition of DNA molecules is studied in an exactly solvable formalism with the Morse and Deng–Fan potentials for the interstrand hydrogen bonds of nucleotide base pairs. It is shown that although the two potentials have different short-range behaviors, the thermodynamic quantities of the DNA system in these potentials enjoy the same scaling laws with the associated critical exponents, which are explicitly calculated. These exactly solvable DNA models are shown to exhibit a phase transition of the second order and the results of the analysis agree with previous studies.

scholarly journals Ribosome Profiling Reveals HSP90 Inhibitor Effects on Stage-Specific Protein Synthesis in Leishmania donovani

mSystems ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Eugenia Bifeld ◽  
Stephan Lorenzen ◽  
Katharina Bartsch ◽  
Juan-José Vasquez ◽  
T. Nicolai Siegel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Leishmania Donovani ◽  
Specific Protein ◽  
Ribosome Profiling ◽  
Severe Illness ◽  
Content Type ◽  
Hsp90 Activity

ABSTRACT The 90-kDa heat shock protein (HSP90) of eukaryotes is a highly abundant and essential chaperone required for the maturation of regulatory and signal proteins. In the protozoan parasite Leishmania donovani, causative agent of the fatal visceral leishmaniasis, HSP90 activity is essential for cell proliferation and survival. Even more importantly, its inhibition causes life cycle progression from the insect stage to the pathogenic, mammalian stage. To unravel the molecular impact of HSP90 activity on the parasites’ gene expression, we performed a ribosome profiling analysis of L. donovani, comparing genome-wide protein synthesis patterns in the presence and absence of the HSP90-specific inhibitor radicicol and an ectopically expressed radicicol-resistant HSP90 variant. We find that ribosome-protected RNA faithfully maps open reading frames and represents 97% of the annotated protein-coding genes of L. donovani. Protein synthesis was found to correlate poorly with RNA steady-state levels, indicating a regulated translation as primary mechanism for HSP90-dependent gene expression. The results confirm inhibitory effects of HSP90 on the synthesis of Leishmania proteins that are associated with the pathogenic, intracellular stage of the parasite. Those include heat shock proteins, redox enzymes, virulence-enhancing surface proteins, proteolytic pathways, and a complete set of histones. Conversely, HSP90 promotes fatty acid synthesis enzymes. Complementing radicicol treatment with the radicicol-resistant HSP90rr variant revealed important off-target radicicol effects that control a large number of the above-listed proteins. Leishmania lacks gene-specific transcription regulation and relies on regulated translation instead. Our ribosome footprinting analysis demonstrates a controlling function of HSP90 in stage-specific protein synthesis but also significant, HSP90-independent effects of the inhibitor radicicol. IMPORTANCE Leishmania parasites cause severe illness in humans and animals. They exist in two developmental stages, insect form and mammalian form, which differ in shape and gene expression. By mapping and quantifying RNA fragments protected by protein synthesis complexes, we determined the rates of protein synthesis for >90% of all Leishmania proteins in response to the inhibition of a key regulatory protein, the 90-kDa heat shock protein. We find that Leishmania depends on a regulation of protein synthesis for controlling its gene expression and that heat shock protein 90 inhibition can trigger the developmental program from insect form to mammalian form of the pathogen.

Cooperative vibrational properties of hydrogen bonds in Watson–Crick DNA base pairs

2017 ◽  
Vol 41 (20) ◽  
pp. 12104-12109 ◽  
Author(s):  
Yulei Shi ◽  
Wanrun Jiang ◽  
Zhiyuan Zhang ◽  
Zhigang Wang
Keyword(s):  
Hydrogen Bonds ◽  
Vibrational Properties ◽  
Base Pairs ◽  
Dna Base ◽  
Dna Base Pairs

For the AT pair, Symst and Strech peaks further shift toward the red, giving the H-bonds an amplified effect (orange arrows).

Three-centre C—H...O hydrogen bonds in the DNA minor groove: analysis of oligonucleotide crystal structures

1999 ◽  
Vol 55 (12) ◽  
pp. 2005-2012 ◽  
Author(s):  
Anirban Ghosh ◽  
Manju Bansal
Keyword(s):  
Hydrogen Bonds ◽  
Crystal Structures ◽  
Base Pair ◽  
Minor Groove ◽  
Local Geometry ◽  
Data Sets ◽  
Base Pairs ◽  
Dna Minor Groove ◽  
Close Proximity ◽  
Using Data

AA·TT and GA·TC dinucleotide steps in B-DNA-type oligomeric crystal structures and in protein-bound DNA fragments (solved using data with resolution <2.6 Å) show very small variations in their local dinucleotide geometries. A detailed analysis of these crystal structures reveals that in AA·TT and GA·TC steps the electropositive C2—H2 group of adenine is in very close proximity to the keto O atoms of both the pyrimidine bases in the antiparallel strand of the duplex structure, suggesting the possibility of intra-base pair as well as cross-strand inter-base pair C—H...O hydrogen bonds in the DNA minor groove. The C2—H2...O2 hydrogen bonds in the A·T base pairs could be a natural consequence of Watson–Crick pairing. However, the cross-strand interactions between the bases at the 3′-end of the AA·TT and GA·TC steps obviously arise owing to specific local geometry of these steps, since a majority of the H2...O2 distances in both data sets are considerably shorter than their values in the uniform fibre model (3.3 Å) and many are even smaller than the sum of the van der Waals radii. The analysis suggests that in addition to already documented features such as the large propeller twist of A·T base pairs and the hydration of the minor groove, these C2—H2...O2 cross-strand interactions may also play a role in the narrowing of the minor groove in A-tract regions of DNA and help explain the high structural rigidity and stability observed for poly(dA)·poly(dT).

scholarly journals Using mitoribosomal profiling to investigate human mitochondrial translation

2018 ◽  
Vol 2 ◽  
pp. 116
Author(s):  
Fei Gao ◽  
Maria Wesolowska ◽  
Reuven Agami ◽  
Koos Rooijers ◽  
Fabricio Loayza-Puch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Codon Position ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Synthesis ◽  
Mitochondrial Translation ◽  
Base Pairs ◽  
Suboptimal Structure ◽  
Human Counterpart ◽  
Steady State Levels

Background: Gene expression in human mitochondria has various idiosyncratic features. One of these was recently revealed as the unprecedented recruitment of a mitochondrially-encoded tRNA as a structural component of the large mitoribosomal subunit. In porcine particles this is mt-tRNAPhe whilst in humans it is mt-tRNAVal. We have previously shown that when a mutation in mt-tRNAVal causes very low steady state levels, there is preferential recruitment of mt-tRNAPhe. We have investigated whether this altered mitoribosome affects intra-organellar protein synthesis. Methods: By using mitoribosomal profiling we have revealed aspects of mitoribosome behaviour with its template mt-mRNA under both normal conditions as well as those where the mitoribosome has incorporated mt-tRNAPhe. Results: Analysis of the mitoribosome residency on transcripts under control conditions reveals that although mitochondria employ only 22 mt-tRNAs for protein synthesis, the use of non-canonical wobble base pairs at codon position 3 does not cause any measurable difference in mitoribosome occupancy irrespective of the codon. Comparison of the profile of aberrant mt-tRNAPhe containing mitoribosomes with those of controls that integrate mt-tRNAVal revealed that the impaired translation seen in the latter was not due to stalling on triplets encoding either of these amino acids. The alterations in mitoribosome interactions with start codons was not directly attributable to the either the use of non-cognate initiation codons or the presence or absence of 5’ leader sequences, except in the two bicistronic RNA units, RNA7 and RNA14 where the initiation sites are internal. Conclusions: These data report the power of mitoribosomal profiling in helping to understand the subtleties of mammalian mitochondrial protein synthesis. Analysis of profiles from the mutant mt-tRNAVal cell line suggest that despite mt-tRNAPhe being preferred in the porcine mitoribosome, its integration into the human counterpart results in a suboptimal structure that modifies its interaction with mt-mRNAs.

Synthesis of novel guttiferone A derivatives: In-vitro evaluation toward Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani

2013 ◽  
Vol 65 ◽  
pp. 284-294 ◽  
Author(s):  
Yann Fromentin ◽  
Nicolas Gaboriaud-Kolar ◽  
Bruno Ndjakou Lenta ◽  
Jean Duplex Wansi ◽  
Didier Buisson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Trypanosoma Brucei ◽  
Leishmania Donovani ◽  
In Vitro Evaluation

scholarly journals Frequency and hydrogen bonding of nucleobase homopairs in small molecule crystals

2020 ◽  
Vol 48 (15) ◽  
pp. 8302-8319
Author(s):  
Małgorzata Katarzyna Cabaj ◽  
Paulina Maria Dominiak
Keyword(s):  
Hydrogen Bonding ◽  
Hydrogen Bonds ◽  
Crystal Structures ◽  
Small Molecule ◽  
Base Pair ◽  
Base Pairs ◽  
Standard Pattern ◽  
Planar Structures ◽  
Structural Database ◽  
Derivatives Of

Abstract We used the high resolution and accuracy of the Cambridge Structural Database (CSD) to provide detailed information regarding base pairing interactions of selected nucleobases. We searched for base pairs in which nucleobases interact with each other through two or more hydrogen bonds and form more or less planar structures. The investigated compounds were either free forms or derivatives of adenine, guanine, hypoxanthine, thymine, uracil and cytosine. We divided our findings into categories including types of pairs, protonation patterns and whether they are formed by free bases or substituted ones. We found base pair types that are exclusive to small molecule crystal structures, some that can be found only in RNA containing crystal structures and many that are native to both environments. With a few exceptions, nucleobase protonation generally followed a standard pattern governed by pKa values. The lengths of hydrogen bonds did not depend on whether the nucleobases forming a base pair were charged or not. The reasons why particular nucleobases formed base pairs in a certain way varied significantly.

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