14 What RNA world ?? Ancestral polypeptides likely participated in the origins of translation

A widespread consensus holds that protein synthesis according to a genetic code was launched entirely by sophisticated RNA molecules that played both coding and functional roles. This belief persists, unsupported by phylogenetic evidence for ancestral ribozymes that catalyzed either amino acid activation or tRNA aminoacylation. By contrast, we have adduced strong experimental evidence that the most highly conserved portions of contemporary aminoacyl-tRNA synthetases (aaRS) accelerate both reactions well in excess of rates achieved by RNA aptomers derived from combinatorial libraries and of rates required for primordial protein synthesis. Such ancestral enzymes, or “Urzymes”, characterized for Class I (TrpRS (Pham et al., 2010, 2007) and LeuRS (Collier et al., 2013); 130 residues) and Class II (HisRS; 120–140 residues; (Li et al., 2011)) synthetases generally have promiscuous amino acid specificities, whereas ATP and cognate tRNA affinities are within an order of magnitude of those for contemporary enzymes. These characteristics match or exceed expectations for the primordial catalysts necessary to launch protein synthesis. Structural hierarchies in Class I and II aaRS also exhibit plateaus of increasing enzymatic activity, suggesting that catalysis by peptides similar to the Aleph motif identified by Trifonov (Sobolevsky et al.) may have been both necessary and sufficient to launch protein synthesis. Sense/antisense alignments of TrpRS and HisRS Urzyme coding sequences reveal unexpectedly high middle-base complementarity that increases in reconstructed ancestral nodes (Chandrasekaran et al.), consistent with the proposal of Rodin and Ohno (Rodin & Ohno, 1995). Thus, these ancestors were likely coded by opposite strands of the same gene, favoring simultaneous expression of aaRS activating both hydrophobic (core) and hydrophilic (surface) amino acids. Our results support the view that aaRS coevolved with cognate tRNAs from a much earlier stage than that envisioned under the RNA World hypothesis, and that their descendants make up appreciable portions of the proteome.     

小??和凤头??越冬潜水行为及差异

2013年10月—2014年3月,采用焦点动物法观察了小??Tachybaptus ruficollis和凤头??Podiceps cristatus的越冬潜水行为。小??的平均潜水持续时间和暂停持续时间分别为(13.84 s±5.66 s)(n=1593)和(12.24 s±9.71 s)(n=1504),凤头??为(21.72 s±9.65 s)(n=793)和(17.88 s±11.68 s)(n=728),均在越冬不同时期和昼间不同时段有所差异。小??(1.13)和凤头??(1.21)的潜水效率均较低,小??的潜水效率更为稳定。2个物种中,仅小??的暂停持续时间与前一次和后一次的潜水有极显著相关性。2种??在潜水持续时间长及潜水效率高的时段均相似,但也产生了"错峰"等分化现象。本文还验证了潜水持续时间随体型增大而增长,温度下降会导致潜水效率下降等规律。     

娇俏的小??

正说起城市里的鸟类,在许多城市水体中,我们都会看到一种喜爱在水中时而游弋、时而潜水的小鸭子般的小鸟,其实它们可不是鸭子,它们的真名叫做小??。相信很多朋友依旧对这两个汉字犯晕,这次再强调一下,读音是?(pì)?(tī)。这两个字可不是现代鸟类学家生造出来的,而是古汉字里就有的,有时候也会被写作"鷿?"。而今天,     

Non-coding RNA and antisense RNA. Nature's trash or treasure?

Although control of cellular function has classically been considered the responsibility of proteins, research over the last decade has elucidated many roles for RNA in regulation of not only the proteins that control cellular functions but also for the cellular functions themselves. In parallel to this advancement in knowledge about the regulatory roles of RNA there has been an explosion of knowledge about the role that epigenetics plays in controlling not only long-term cellular fate but also the short-term regulatory control of genes. Of particular interest is the crossover between these two worlds, a world where RNA can act out its part and subsequently elicit chromatin modifications that alter cellular function. Two main categories of RNA are examined here, non-coding RNA and antisense RNA both of which perform vital functions in controlling numerous genes, proteins and RNA itself. As the activities of non-coding and antisense RNA in both normal and aberrant cellular function are elucidated, so does the number of possible targets for pharmacopeic intervention.     

‘RNA walk’ a novel approach to study RNA–RNA interactions between a small RNA and its target

In this study we describe a novel method to investigate the RNA–RNA interactions between a small RNA and its target that we termed ‘RNA walk’. The method is based on UV-induced AMT cross-linking in vivo followed by affinity selection of the hybrid molecules and mapping the intermolecular adducts by RT–PCR or real-time PCR. Domains carrying the cross-linked adducts fail to efficiently amplify by PCR compared with non-cross-linked domains. This method was calibrated and used to study the interaction between a special tRNA-like molecule (sRNA-85) that is part of the trypanosome signal recognition particle (SRP) complex and the ribosome. Four contact sites between sRNA-85 and rRNA were identified by ‘RNA walk’ and were further fine-mapped by primer extension. Two of the contact sites are expected; one contact site mimics the interaction of the mammalian Alu domain of SRP with the ribosome and the other contact sites include a canonical tRNA interaction. The two other cross-linked sites could not be predicted. We propose that ‘RNA walk, is a generic method to map target RNA small RNAs interactions in vivo.     

甘肃省鸟类新记录——角??

正2020年1月5日11∶30,在甘肃省张掖市张掖国家湿地公园(100°26'16″E,38°58'18″N,海拔1 462 m)进行鸟类调查时,发现3只角??Podiceps auritus,并拍摄到其在水中觅食、追逐和嬉戏的清晰照片(图1)。经查阅《中国鸟类野外手册》(约翰·马敬能等,2000)、《中国鸟类分类与分布名录(第三版)》(郑光美,2017)等相关文献资料,确认该鸟为甘肃省分布新记录,该发现为了解其地理分布提供了基础资料。     

Solubility and Stability of ??-Cyclodextrin?CTerpineol Inclusion Complex as Affected by Water

In the present work, inclusion complexes of α-terpineol (Terp) and β-cyclodextrin (BCD) were prepared by the coprecipitation method. Phase solubility studies were performed and thermodynamic parameters involved in the complex formation were calculated. The solubility of Terp increased linearly as the concentration of BCD was increased, confirming the 1:1 stoichiometry of the complex. The stability constants decreased along with increasing temperature. The negative value of the enthalpy and of the Gibbs free energy demonstrated that the process is exothermic and spontaneous. Since complexation gives more ordered systems, the negative value obtained for the entropy change evidenced the encapsulation of Terp. Terp was completely encapsulated in BCD at the preparation conditions and studied molar ratios, as confirmed in the freeze-dried samples by differential scanning calorimeter. The presence of Terp greatly modified the BCD water sorption curves, and the amount of adsorbed water was lower for the complexes. The limited water solubility of Terp could be overcome by the formation of BCD inclusion complexes, and the complexes were stable at different storage conditions (relative humidities 11–97% and 25 °C). The obtained phase solubility data are useful for food or pharmaceutical products formulation involving cyclodextrins and stability predictions.     

Structural Aspects of the Antiparallel and Parallel Duplexes Formed by DNA, 2’-O-Methyl RNA and RNA Oligonucleotides

This study investigated the influence of the nature of oligonucleotides on the abilities to form antiparallel and parallel duplexes. Base pairing of homopurine DNA, 2’-O-MeRNA and RNA oligonucleotides with respective homopyrimidine DNA, 2’-O-MeRNA and RNA as well as chimeric oligonucleotides containing LNA resulted in the formation of 18 various duplexes. UV melting, circular dichroism and fluorescence studies revealed the influence of nucleotide composition on duplex structure and thermal stability depending on the buffer pH value. Most duplexes simultaneously adopted both orientations. However, at pH 5.0, parallel duplexes were more favorable. Moreover, the presence of LNA nucleotides within a homopyrimidine strand favored the formation of parallel duplexes.     

Competition between α and β globin messenger RNA

Addition to an unfractionated reticulocyte lysate of either α or β globin mRNA or reticulocyte initiation factors does not alter the overall rate of globin synthesis. Addition of β mRNA results in enhanced synthesis of β product and decreased production of α; conversely, addition of α mRNA results in enhanced synthesis of α globin and decreased production of β. We conclude that the amount of any putative α mRNA or β mRNA-specific factor does not normally limit the rate of synthesis of α or β chains; rather, the two mRNAs compete for some non-specific rate-limiting component of chain initiation.     

Regulation of RNA function by aminoacylation and editing?

The chemical modification of nucleic acids is a ubiquitous phenomenon. Aminoacylation of tRNAs by aminoacyl-tRNA synthetases (ARSs) is a reaction essentially devoted to protein synthesis but it is used also as an emergency mechanism to recycle stalled ribosomes, and it is required for genome replication in some RNA viruses. In several aminoacyl-tRNA synthetases a correction mechanism known as editing is present to prevent aminoacylation errors. Genome data reveal a growing number of open reading frames encoding ARS-like proteins. This strongly suggests the existence of a widespread and nonconventional machinery for aminoacylation and editing. Here we review the different biological functions of aminoacylation and editing; also we propose an evolutionary scenario for the origin of these two reactions, and hypothesize an extant role for RNA charging and editing outside the genetic code.     

Recombination and RNA processing: a common strand?

Genetic recombination is a basic cellular process required for altering genome structure. The RecA protein of Escherichia coli has a central role in homologous recombination, and a eukaryotic protein with similar properties has been discovered in the yeast Saccharomyces cerevisiae. Unexpectedly, this RecA-like protein has additional biochemical activities, and its function may not be restricted to recombination.     

Human RNaseP RNA and nucleolar 7-2 RNA share conserved ‘To’ antigen-binding domains

RNase P in both prokaryotes and eukaryotes is a ribonucleoprotein that cleaves tRNA precursors to generate the 5 termini of the mature tRNAs. Many patients with autoimmune diseases produce antibodies against a 40 kDa protein (designatedTo orTh antigen) which is an integral component of eukaryotic RNaseP as well as nucleolar 7-2 RNP which is identical to the mitochondrial RNA processing (MRP) RNP. Interestingly, theTo antigen found in human cells and the C5 protein, the only protein component ofE. coli RNaseP, are antigenically related. In this study, we show that a 56 nucleotide-long sequence, corresponding to nucleotides 20–75 near the 5 end of human RNaseP RNA, is sufficient to bind theTo antigen. We previously showed that the humanTo antigen binds to a short distinct structural domain near the 5 end of human 7-2/MRP RNA. There is no obvious primary sequence homology between theTo antigen binding sites in RNaseP RNA and 7-2/MRP RNA; however, these sequences are capable of assuming a similar secondary structure which corresponds to the recently proposed cage structure for RNaseP RNAs and 7-2/MRP RNA (Forster and Altman (1989) Cell 62: 407–409). These data are supportive of the idea that these two RNAs may have evolved from a common progenitor molecule.     

Pre-aggregated A??1?C42 peptide increases tau aggregation and hyperphosphorylation after short-term application

Neuritic amyloid plaques and neurofibrillary tangles, consisting of hyperphosphorylated tau protein, are the hallmarks of Alzheimer disease. It is not clear so far, how both structures are functionally and physiologically connected. We have investigated the role of Aβ1-42 on hyperphosphorylation and aggregation of tau in SY5Y cells by transfection and overexpression with two tau constructs, a shortened wildtype tau (2N4R) and a point mutation tau (P301L), found in fronto-temporal dementia. It was found that the tau protein becomes hyperphosphorylated and forms large aggregates inside cells, visualized by immunofluorescence, after short incubation of 90 min with preaggregated Aβ1-42. In Addition, Aβ1-42 caused a decrease of tau solubility in both tau constructs in this relatively short time period. Taken together, these experiments suggest that pathological preaggregated Aβ1-42 in physiological concentrations quickly induces hyperphosphorylation and pathological structural changes of tau protein and thereby directly linking the 'amyloid hypothesis' to tau pathology, observed in Alzheimer disease.     

Decreased RNA, and Increased RNA Oxidation, in Ribosomes from Early Alzheimer’s Disease

All cells rely on efficient protein synthesis in order to maintain cellular homeostasis. Recent studies from our laboratory indicate that declines in protein synthesis and ribosome function occur in the earliest stage of Alzheimer’s disease (AD). Additional studies indicate a potential role for ribosomal RNA oxidation as a potential mediator of decreased protein synthesis in AD. The ribosome is a complex of proteins and nucleic acids that mediates all protein synthesis. At present it is unclear if significant alterations in ribosomal RNA occurs within the ribosome complex during the progression of AD. In this study we examined the amount of ribosomal RNA in the different ribosomal fractions generated from control subjects, individuals with mild cognitive impairment (MCI), and individuals with AD. Studies were conducted in the inferior parietal lobule of each subject. Together, these data demonstrate that during the progression of AD there is a gross decline in the amount of ribosomal RNA within the ribosome complex. Additionally, these studies provide evidence for gross elevations in RNA oxidation within the ribosome complex of MCI and AD. Together, these data strongly suggest a role for RNA alterations within the ribosome as a mediator of decreased protein synthesis in both MCI and AD.     

Prebiotic co-evolution of self-replication and translation or RNA world?

A prebiotic scenario is proposed, based on the recent "domain hypothesis" model (Lahav, 1989, J. molec. Evol. 29, 475-479), suggested for domain propagation of RNA-like molecules in a fluctuating environment. The same system is suggested now not only for the evolution of ribozymes, but also for the evolution of directed peptide synthesis, as follows: Short, self-structured strands (termed prebioectons), each possessing a templatable domain which is chargeable by an amino acid, are the predecessors of tRNA (proto-tRNA). Complementary domains are formed on these prebioectons during an environmental cycle such as wetting-drying, followed by their dissociation from their template domain and ligation, to form the predecessor of mRNA (proto-mRNA). The evolution of directed peptide synthesis is suggested to be based on the ability of the charged prebioectons to attach preferentially to their complementary domains on the proto-mRNA. Two stages of this process are envisioned, namely: (a) Template-directed, random peptide synthesis taking place when non-specifically-charged prebioectons are sequentially attached each to its complementary domain on the proto-mRNA, followed by peptide bond formation. (b) Template-and-sequence-directed peptide synthesis, which can be realized after the "invention" of a catalytic molecule capable of specifically charging a proto-tRNA by an amino acid; this is the crucial evolutionary stage, where a crude genetic code becomes functional. Gradually, catalytic peptides and ribozymes are selected for their functions and evolve, while being encoded in the primitive "memory" of the emerging system. Thus, rather than the RNA monopoly postulated by the RNA World hypothesis, an early co-evolution of primitive enzymes and ribozymes is suggested.(ABSTRACT TRUNCATED AT 250 WORDS)