RNA biology

Yablokov A.V., Ostroumov S.A.  Molecular-Genetic Level. In: Conservation of Living Nature and Resources. Springer, Berlin, Heidelberg, (1991) pp 18-38;
(Chapter 2);
About this chapter
Cite this chapter as:
Yablokov A.V., Ostroumov S.A. (1991) Molecular-Genetic Level. In: Conservation of Living Nature and Resources. Springer, Berlin, Heidelberg. pp 18-38;  https://doi.org/10.1007/978-3-642-75376-3_3
https://www.academia.edu/71478685/ ;
• DOI: 10.1007/978-3-642-75376-3_3
• pp 18-38; Chapter length: 21 pages;

• DOI https://doi.org/10.1007/978-3-642-75376-3_3

• Publisher Name Springer, Berlin, Heidelberg;

• Print ISBN 978-3-642-75378-7

• Online ISBN 978-3-642-75376-3

• eBook PackagesSpringer Book Archive



DOI https://doi.org/10.1007/978-3-642-75376-3_12 ;

• Publisher Name Springer, Berlin, Heidelberg;

• Print ISBN 978-3-642-75378-7;

• Online ISBN 978-3-642-75376-3;
Chapter 2;

Conservation of Living Nature and Resources, pp 18-38;
Molecular-Genetic Level;
• Alexey V. Yablokov, 
• Sergey A. Ostroumov,

Moscow State University, Faculty of Biology, Moscow 119991; Russia;

, Abstract (Chapter 2):
Abstract
Many problems of conservation occur at the molecular-genetic level of life systems. The elementary units at this level are genes represented by segments of DNA (or RNA in some viruses); the elementary events at this level are convariant reduplications of genes. Processes of realization of information stored in DNA involve the functioning of the biochemical machinery of the cell.
Keywords
Genes, DNA, RNA, cell, Sewage Sludge, Anthropogenic Factor, Aryl Hydrocarbon Hydroxylase, Biochemical Machinery, Redox Chain,




Lot of info on the entire book is here:
https://www.academia.edu/45623432/;

https://rd.springer.com/book/10.1007/978-3-642-75376-3



About this chapter
Cite this chapter as:
Yablokov A.V., Ostroumov S.A. (1991) Molecular-Genetic Level. In: Conservation of Living Nature and Resources. Springer, Berlin, Heidelberg. pp 18-38;  https://doi.org/10.1007/978-3-642-75376-3_3
• DOI: 10.1007/978-3-642-75376-3_3
• pp 18-38; Chapter length: 21 pages;

• DOI https://doi.org/10.1007/978-3-642-75376-3_3

• Publisher Name Springer, Berlin, Heidelberg;

• Print ISBN 978-3-642-75378-7

• Online ISBN 978-3-642-75376-3

• eBook PackagesSpringer Book Archive



DOI https://doi.org/10.1007/978-3-642-75376-3_12 ;

• Publisher Name Springer, Berlin, Heidelberg;

• Print ISBN 978-3-642-75378-7;

• Online ISBN 978-3-642-75376-3;
Chapter 2;

Conservation of Living Nature and Resources, pp 18-38;
Molecular-Genetic Level;
• Alexey V. Yablokov, 
• Sergey A. Ostroumov,

Moscow State University, Faculty of Biology, Moscow 119991; Russia;

, Abstract (Chapter 2):
Abstract
Many problems of conservation occur at the molecular-genetic level of life systems. The elementary units at this level are genes represented by segments of DNA (or RNA in some viruses); the elementary events at this level are convariant reduplications of genes. Processes of realization of information stored in DNA involve the functioning of the biochemical machinery of the cell.
Keywords
Genes, DNA, RNA, cell, Sewage Sludge, Anthropogenic Factor, Aryl Hydrocarbon Hydroxylase, Biochemical Machinery, Redox Chain,




Lot of info on the entire book is here:
https://www.academia.edu/45623432/;

https://rd.springer.com/book/10.1007/978-3-642-75376-3 ;

The endoribonuclease toxins of the E. coli toxin-antitoxin systems arrest bacterial growth and protein synthesis by targeting cellular mRNAs. As an exception, E. coli MazF was reported to cleave also 16S rRNA at a single site and separate an anti-Shine-Dalgarno sequence-containing RNA fragment from the ribosome. We noticed extensive rRNA fragmentation in response to induction of the toxins MazF and MqsR, which suggested that these toxins can cleave rRNA at multiple sites. We adapted differential RNAsequencing to map the toxin-cleaved 5 0 -and 3 0 -ends. Our results show that the MazF and MqsR cleavage sites are located within structured rRNA regions and, therefore, are not accessible in assembled ribosomes. Most of the rRNA fragments are located in the aberrant ribosomal subunits that accumulate in response to toxin induction and contain unprocessed rRNA precursors. We did not detect MazF-or MqsR-cleaved rRNA in stationary phase bacteria and in assembled ribosomes. Thus, we conclude that MazF and MqsR cleave rRNA precursors before the ribosomes are assembled and potentially facilitate the decay of surplus rRNA transcripts during stress.

A major obstacle for effective utilization of therapeutic oligonucleotides such as siRNA, antisense, antimiRs etc. is to deliver them specifically to the target tissues. Toward this goal, nucleic acid aptamers are re-emerging as a prominent class of biomolecules capable of delivering target specific therapy and therapeutic monitoring by various molecular imaging modalities. This class of short oligonucleotide ligands with high affinity and specificity are selected from a large nucleic acid pool against a molecular target of choice. Poor cellular uptake of therapeutic oligonucleotides impedes gene-targeting efficacy in vitro and in vivo. In contrast, aptamer-oligonucleotide chimeras have shown the capacity to deliver siRNA, antimiRs, small molecule drugs etc. toward various targets and showed very promising results in various studies on different diseases models. However, to further improve the bio-stability of such chimeric conjugates, it is important to introduce chemically-modifie...

Due to the presence of a diverse array of metabolites, no standard method of RNA isolation is available for plants. We noted that polysaccharide and polyphenol contents of cardamom tissues critically hinder the RNA extraction procedure. Hence, we attempted several methods for obtaining intact mRNA and small RNA from various cardamom tissues. It was found that protocols involving a combination of commercial kits and conventional CTAB (cetyl trimethylammonium bromide) methods yielded RNA with good purity, higher yield, and good integrity. The total RNA isolated through this approach was found to be amenable for transcriptome and small RNA analysis through next-generation sequencing platforms. Molecular techniques such as next-generation sequencing (NGS) 1 have been established as a highly sensitive and efficient method for small RNA and transcriptome analysis. However, the poor-quality RNA samples interfere with the sequencing procedure. The RNA extraction strategy varies in different species based on the levels of secondary metabolites and polysaccharides [1]. There are previous reports on extracting high-purity RNA from plants [2–6], but these methods did not generate intact RNA from tissues of car-damom (Elettaria cardamomum Maton), the plant of our interest. Hence, this study aimed to find out the most ideal protocol for isolation of high-quality RNA from different tissues for downstream applications such as small RNA sequencing and transcriptome analysis using NGS platforms. The plant tissues used for RNA isolation were collected from the Jawaharlal Nehru Tropical Botanic Garden & Research Institute (JNTBGRI) cardamom germplasm conservatory (accession no. CT9). Fresh leaves, stems, flowers, flower buds, and young fruits were collected, washed well with distilled water, and covered with sterilized aluminum foil to avoid RNase contamination and were immediately placed in liquid nitrogen. The tissues remained as such until further processing. Solutions for RNA isolations were treated with 0.01% diethylpy-rocarbonate (DEPC, Sigma) and then incubated overnight at room temperature. The treated solutions were autoclaved for 20 min to degrade the traces of DEPC. All of the reagents used in the protocols were prepared using the DEPC-treated water to inactivate RNases. Materials such as mortar, pestle, and spatula were also treated with DEPC, incubated overnight, wrapped in aluminum foil, and baked at 180°C for 5 h. The workbench for RNA isolation, pipettes, all plasticwares, and centrifuge were wiped twice with RNaseZap (Ambion) to remove RNase present on the surface. Frequent swabbing of gloves with RNaseZap solution avoids RNase contamination. Electrophoresis gel tank, gel comb, and gel tray were soaked in buffer (0.1 M NaOH and 100 mM ethylenediaminete-traacetic acid) for 2 h and rinsed well with DEPC-treated water. The tissues were subjected to nine RNA isolation methods: modified CTAB (cetyl trimethylammonium bromide) method (hereafter referred to as CTAB method) [7], TRIzol method [8], TRIzol with sodium sulfite method [9], Qiagen's RNeasy Plant and miRNeasy Mini Kits, PureLink RNA Mini Kit (Ambion), and the combined methods of PureLink RNA Mini Kit and CTAB, miRNeasy Mini Kit and CTAB (Dongyan Zhao, Michigan State University, personal communication), and RNeasy Plant Mini Kit and CTAB. The RNA isolation method based on CTAB implemented in this study was a modification of the previously described protocol [7] with a change in the amount of initial sample (100 mg of leaves and stems or 250 mg of flowers, flower buds, and young fruits), incubation time (30 min for leaves and stems or 40 min

The covalent modification of RNA molecules is a pervasive feature of all classes of RNAs and has fundamental roles in the regulation of several cellular processes. Mapping the location of RNA modifications transcriptome-wide is key to unveiling their role and dynamic behaviour, but technical limitations have often hampered these efforts. Nanopore direct RNA sequencing is a third-generation sequencing technology that allows the sequencing of native RNA molecules, thus providing a direct way to detect modifications at single-molecule resolution. Despite recent advances, the analysis of nanopore sequencing data for RNA modification detection is still a complex task that presents many challenges. Many works have addressed this task using different approaches, resulting in a large number of tools with different features and performances. Here we review the diverse approaches proposed so far and outline the principles underlying currently available algorithms.

The genome of most prokaryotes gives rise to surprisingly complex transcriptomes, comprising not only protein-coding mRNAs, often organized as operons, but also harbors dozens or even hundreds of highly structured small regulatory RNAs and unexpectedly large levels of anti-sense transcripts. Comprehensive surveys of prokaryotic transcriptomes and the need to characterize also their non-coding components is heavily dependent on computational methods and workflows, many of which have been developed or at least adapted specifically for the use with bacterial and archaeal data. This review provides an overview on the state-of-the-art of RNA bioinformatics focusing on applications to prokaryotes.

Small RNAs (sRNAs) play a pivotal role in bacterial gene regulation. However, the sRNAs of the vast majority of bacteria with sequenced genomes still remain unknown since sRNA genes are usually difficult to recognize and thus not annotated. Here, expression of seven sRNAs (BjrC2a, BjrC2b, BjrC2c, BjrC68, BjrC80, BjrC174 and BjrC1505) predicted by genome comparison of Bradyrhizobium and Rhodopseudomonas members, was verified by RNA gel blot hybridization, microarray and deep sequencing analyses of RNA from the soybean symbiont Bradyrhizobium japonicum USDA 110. BjrC2a, BjrC2b and BjrC2c belong to the RNA family RF00519, while the other sRNAs are novel. For some of the sRNAs we observed expression differences between free-living bacteria and bacteroids in root nodules. The amount of BjrC1505 was decreased in nodules. By contrast, the amount of BjrC2a, BjrC68, BjrC80, BjrC174 and the previously described 6S RNA was increased in nodules, and accumulation of truncated forms of these sRNAs was observed. Comparative genomics and deep sequencing suggest that BjrC2a is an antisense RNA regulating the expression of inositol-monophosphatase. The analyzed sRNAs show a different degree of conservation in Rhizobiales, and expression of homologs of BjrC2, BjrC68, BjrC1505, and 6S RNA was confirmed in the free-living purple bacterium Rhodopseudomonas palustris 5D.

Short hairpin RNAs (shRNAs) are widely used for gene knockdown by inducing the RNA interference (RNAi) mechanism, both for research and therapeutic purposes. The shRNA precursor is processed by the RNase III-like enzyme Dicer into biologically active small interfering RNA (siRNA). This effector molecule subsequently targets a complementary mRNA for destruction via the Argonaute 2 (AGO2) complex. The cellular role of Dicer concerns the processing of pre-miRNAs into mature microRNA (miRNA). Recently, a non-canonical pathway was reported for the biogenesis of miR-451, which bypasses Dicer and is processed instead by the slicer activity of AGO2, followed by the regular AGO2-mediated mRNA targeting step. Interestingly, shRNA designs that are characterized by a relatively short basepaired stem also bypass Dicer to be processed by AGO2. We named this design AgoshRNA as these molecules depend on AGO2 both for processing and silencing activity. In this study, we investigated diverse mechanis...

Cap-dependent translation initiation begins by assembly of a pre-initiation ribosomal complex that scans the 5ʹ Untranslated Region in order to localise the start codon. During this process, RNA secondary structures are melted by RNA helicases. Guenther et al reported that the yeast helicase Ded1, an orthologue of the mammalian DDX3 helicase, is responsible for this activity. When Ded1 is nonfunctional, RNA structures in the 5ʹUTR promote translation initiation on Alternative Translation Initiation Sites (ATIS) lead to uORF translation and consequently down-regulation of the main ORF. This mechanism is driven by the sole presence of RNA secondary structures located downstream of ATIS. Translation initiation mediated by RNA structures is found in other messenger RNAs. We propose to name this novel mechanism STructure-Assisted-RNA-Translation or START.

Keyords: U1snRNP, 5'splice site, alternative splicing, pre-mRNA processing Abbreviations: snRNP, small ribonucleoprotein; 5'ss, 5' splice site; 3'ss, 3' splice site; BP, branch-point This manuscript has been published online, prior to printing. Once the issue is complete and page numbers have been assigned, the citation will change accordingly.

TDP-43 is an RNA-binding protein involved in several steps of mRNA metabolism including transcription, splicing and stability. It is also involved in ALS and FTD, neurodegenerative diseases characterized by TDP-43 nuclear depletion. We previously identified TDP-43 as a binder of the downstream element (DSE) of the β-Adducin (Add2) brain-specific polyadenylation site (A4 PAS), suggesting its involvement in pre-mRNA 3' end processing. Here, by using chimeric minigenes, we showed that TDP-43 depletion in HeLa and HEK293 cells resulted in down-regulation of both the chimeric and endogenous Add2 transcripts. Despite having confirmed TDP-43-DSE in vitro interaction, we demonstrated that the in vivo effect was not mediated by the TDP-43-DSE interaction. In fact, substitution of the Add2 DSE with viral E-SV40 and L-SV40 DSEs, which are not TDP-43 targets, still resulted in decreased Add2 mRNA levels after TDP-43 downregulation. In addition, we failed to show interaction between TDP-43 a...

Ribosomal protein S15 is highly conserved among prokaryotes. It plays a pivotal role in the assembly of the central domain of the small ribosomal subunit and regulates its own expression by a feedback mechanism at the translational level. The protein recognizes two RNA targets (rRNA and mRNA) that share only partial similarity. Its interaction with 16S rRNA has been fully characterized, while mRNA interactions and regulatory mechanisms have been extensively studied in E. coli and in T. thermophilus. Recently, we have characterized which aminoacids are involved in E. coli mRNA recognition, using an in vivo assay allowing to identify S15 mutations affecting the S15-mRNA interactions without altering 30S subunit assembly. Here, we address the following questions: Are common determinants used by S15 to recognize its rRNA and mRNA targets? What is the extent of molecular mimicry? Is the regulatory mechanism conserved? Our results indicate that specific recognition of mRNA and rRNA relies on both mimicry and site differentiation. They also highlight the high plasticity of RNA to adapt to evolutionary constraints.

Synthetic small interfering RNA (siRNA) duplexes are widely used to transiently and sequence-specifically disrupt gene expression in mammalian cultured cells. The efficiency and specificity of mRNA cleavage is partly affected by the presence of the nontargeting "passenger" or "sense" siRNA strand, which is required for presentation of the target-complementary or guide siRNA strand to the double-strand-specific RNA silencing protein machinery. We show that siRNA duplexes can be designed that are solely composed of two fully target-complementary guide strands that are sufficiently complementary to each other to form stable duplexes with characteristic 3' overhanging ends. The general feasibility of this approach is documented by transient knockdown of lamin A/C and emerin in HeLa cells. The silencing efficiencies of guide-only siRNA duplexes are comparable to prototypical fully paired passenger/guide duplex siRNAs, even though guide-only siRNA duplexes may contain a significant number of nonWatson-Crick and G/U wobble base pairs. Such siRNA duplexes may offer advantages regarding production costs and specificity of gene silencing.

We had previously proposed that the post-transcriptional regulation through microRNA as a mechanism for incomplete penetrance and variable expressivity, leads to lack of correlation between genotype and phenotype. Here we report the validation of miRNA-target interactions we predicted earlier and demonstrate the regulation of endogenous JAG1 by hsa-miR-214 and hsa-miR-124, and TGFBR2 by hsa-miR-34b*, through luciferase activity of reporter constructs and also the expression levels of the endogenous genes. Using these targets, we have modeled the diploid state for miRNA target site with heterozygosity for the SNP and demonstrate the differential targeting of an otherwise identical 3'UTR. We show that SNP rs8708 (A. G) at the target site of hsa-miR-214 can relieve the repression while an SNP rs11466532 (C. T) enhances the repression of reporter expression by hsa-miR-34b*. We discuss the results in the light of its implications in the context of penetrance of dominant mutations in miRNA targeted genes, using JAG1 as an example. These observations imply that disease causing mutations in JAG1 linked to the SNP rs8708G will be poorly targeted by hsa-miR-214 when present against a normal allele of JAG1 with rs8708A and will show penetrance of JAG1 mutations as Alagille syndrome, while mutant JAG1 linked to rs8708A against rs8708G on the normal allele will show either no disease or much attenuated symptoms and hence exhibit incomplete penetrance.

RNA FAmiLies RNA FAmiLies E pstein-Barr virus (EBV) is a tumorigenic human γ-herpesvirus, which produces several known structured RNAs with functional importance: two are implicated in latency maintenance and tumorigenic phenotypes, EBER1 and EBER2; a viral small nucleolar RNA (v-snoRNA1) that may generate a small regulatory RNA; and an internal ribosomal entry site in the EBNA1 mRNA. A recent bioinformatics and RNA-Seq study of EBV identified two novel EBV non-coding (nc)RNAs with evolutionary conservation in lymphocryptoviruses and likely functional importance. Both RNAs are transcribed from a repetitive region of the EBV genome (the W repeats) during a highly oncogenic type of viral latency. One novel ncRNA can form a massive (586 nt) hairpin, while the other RNA is generated from a short (81 nt) intron and is found in high abundance in EBV-infected cells. Known EBV RNA Families EBER1 and EBER2 are highly structured, non-polyadenylated, and noncoding RNA-Pol III transcripts (Fig. 2) that are each ~170 nt long. High levels of EBER1 and EBER2 are typically found in EBV-infected cells throughout latency. 11,12 The EBERs accumulate in the nucleus to approximately one million copies per cell, where they form stable ribonucleoprotein RNA families in Epstein-Barr virus

The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research. The outcome of this intense research field is the discovery that development, ageing, and stem-cell dependent regeneration but also several diseases including cancer are largely controlled by the epigenetic state of cells. Consequently, this research has already led to the first FDA approved drugs that exploit the gained knowledge to combat disease. In recent years, the ~150 modifications found i...

Deducing generic causal relations between RNA transcript features and protein expression profiles from endogenous gene expression data remains a major unsolved problem in biology. The analysis of gene expression from heterologous genes contributes significantly to solving this problem, but has been heavily biased toward the study of the effect of 5 0 transcript regions and to prokaryotes. Here, we employ a synthetic biology driven approach that systematically differentiates the effect of different regions of the transcript on gene expression up to 240 nucleotides into the ORF. This enabled us to discover new causal effects between features in previously unexplored regions of transcripts, and gene expression in natural regimes. We rationally designed, constructed, and analyzed 383 gene variants of the viral HRSVgp04 gene ORF, with multiple synonymous mutations at key positions along the transcript in the eukaryote S. cerevisiae. Our results show that a few silent mutations at the 5 0 UTR can have a dramatic effect of up to 15 fold change on protein levels, and that even synonymous mutations in positions more than 120 nucleotides downstream from the ORF 5 0 end can modulate protein levels up to 160%-300%. We demonstrate that the correlation between protein levels and folding energy increases with the significance of the level of selection of the latter in endogenous genes, reinforcing the notion that selection for folding strength in different parts of the ORF is related to translation regulation. Our measured protein abundance correlates notably(correlation up to r D 0.62 (pD0.0013)) with mean relative codon decoding times, based on ribosomal densities (Ribo-Seq) in endogenous genes, supporting the conjecture that translation elongation and adaptation to the tRNA pool can modify protein levels in a causal/direct manner. This report provides an improved understanding of transcript evolution, design principles of gene expression regulation, and suggests simple rules for engineering synthetic gene expression in eukaryotes.

G-quadruplexes have recently moved into focus of research in nucleic acids, thereby evolving in scientific significance from exceptional secondary structure motifs to complex modulators of gene regulation. Aptamers (nucleic acid based ligands with recognition properties for a specific target) that form G-quadruplexes may have particular potential for therapeutic applications as they combine the characteristics of specific targeting and G-quadruplex mediated stability and regulation. We have investigated the structure and target interaction properties of one such aptamer: AIR-3 and its truncated form AIR-3A. These RNA aptamers are specific for human interleukin-6 receptor (hIL-6R), a key player in inflammatory diseases and cancer, and have recently been exploited for in vitro drug delivery studies. With the aim to resolve the RNA structure, global shape, RNA:protein interaction site and binding stoichiometry, we now investigated AIR-3 and AIR-3A by different methods including RNA str...

Fragile X syndrome (FXS), the most common cause of inherited intellectual disability, is caused by the loss of expression of the fragile X mental retardation protein (FMRP). FMRP, which regulates the transport and translation of specific mRNAs, uses its RGG box domain to bind mRNA targets that form G-quadruplex structures. One of the FMRP in vivo targets, Shank1 mRNA, encodes the master scaffold proteins of the postsynaptic density (PSD) which regulate the size and shape of dendritic spines because of their capacity to interact with many different PSD components. Due to their effect on spine morphology, altered translational regulation of Shank1 transcripts may contribute to the FXS pathology. We hypothesized that the FMRP interactions with Shank1 mRNA are mediated by the recognition of the G quadruplex structure, which has not been previously demonstrated. In this study we used biophysical techniques to analyze the Shank1 mRNA 3'-UTR and its interactions with FMRP and its phosp...

T he 3' splice site of the influenza A segment 7 transcript is utilized to produce mRNA for the critical M2 ion-channel protein. In solution a 63 nt fragment that includes this region can adopt two conformations: a pseudoknot and a hairpin. In each conformation, the splice site, a binding site for the SF2/ASF exonic splicing enhancer and a polypyrimidine tract, each exists in a different structural context. The most dramatic difference occurs for the splice site. In the hairpin the splice site is between two residues that are involved in a 2 by 2 nucleotide internal loop. In the pseudoknot, however, these bases are canonically paired within one of the pseudoknotted helices. The conformational switching observed in this region has implications for the regulation of splicing of the segment 7 mRNA. A measure of stability of the structures also shows interesting trends with respect to host specificity: avian strains tend to be the most stable, followed by swine and then human.

Processing bodies (P-bodies) are cytoplasmatic mRNP granules containing non-translating mRNas and proteins from the mRNa decay and silencing machineries. The mechanism of P-body assembly has been typically addressed by depleting P-body components. here we apply a complementary approach and establish an automated cell-based assay platform to screen for molecules affecting P-body assembly. From a unique library of compounds derived from myxobacteria, 30 specifically inhibited P-body assembly. Gephyronic acid a (Ga), a eukaryotic protein synthesis inhibitor, showed the strongest effect. Ga also inhibited, under stress conditions, phosphorylation of eIF2α and stress granule formation. Other hits uncovered interesting novel links between P-body assembly, lipid metabolism, and internal organelle physiology. The obtained results provide a chemical toolbox to manipulate P-body assembly and function.

the life of an mRnA molecule begins with transcription and ultimately ends in degradation. in the course of its life, however, mRnA is examined, modified in various ways and transported before being eventually translated into proteins. All these processes are performed by proteins and noncoding RnAs whose complex interplay in the cell contributes to determining the proteome changes and the phenotype of cells. on May 23-26, 2012, over 150 scientists from around the world convened in the sunny shores of Riva del garda, italy, for the workshop entitled: "mRnA fate: Life and Death of mRnA in the Cytoplasm." Sessions included mRnA trafficking, mRnA translational control, RnA metabolism and disease, RnAprotein structures and systems biology of RnA. this report highlights some of the prominent and recurring themes at the meeting and emerging arenas of future research.

Noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long ncRNAs (lncRNAs), are important players in diseases and emerge as novel drug targets. Thus, unraveling the relationships between ncRNAs and other biomedical entities in cells are critical for better understanding ncRNA roles that may eventually help develop their use in medicine. To support ncRNA research and facilitate retrieval of relevant information regarding miRNAs and lncRNAs from the plethora of published ncRNA-related research, we developed DES-ncRNA ( www.cbrc.kaust.edu.sa/des_ncrna ). DES-ncRNA is a knowledgebase containing text- and data-mined information from public scientific literature and other public resources. Exploration of mined information is enabled through terms and pairs of terms from 19 topic-specific dictionaries including, for example, antibiotics, toxins, drugs, enzymes, mutations, pathways, human genes and proteins, drug indications and side effects, mutations, diseases, etc. DES-ncRNA cont...

Musashi1 is an RNA binding protein that controls the neural cell fate, being involved in maintaining neural progenitors in their proliferative state. In particular, its downregulation is needed for triggering early neural differentiation programs. In this study, we profiled microRNA expression during the transition from neural progenitors to differentiated astrocytes and underscored 2 upregulated microRNAs, miR-23a and miR-125b, that sinergically act to restrain Musashi1 expression, thus creating a regulatory module controlling neural progenitor proliferation.

The most dramatic example of RNA editing is found in the mitochondria of trypanosomes. In these organisms, U-insertions/deletions can create mRNAs that are twice as large as the gene that encodes them. Guide RNAs (gRNAs) that are complementary to short stretches of the mature message direct the precise placements of the U residues. The binding of gRNA to mRNA is a fundamental step in RNA editing and understanding the relative importance of the elements that confer affinity and specificity on this interaction is critical to our understanding of the editing process. In this study, we have analyzed the relative binding affinities of two different gRNA/mRNA pairs. The affinity of gA6-14 for its message (ATPase 6) is high, with an apparent K D in the 5-10 nM range. In contrast, gCYb-558 has a low affinity for its cognate mRNA. Deletion of the gRNA U-tail caused a significant reduction in the binding affinity for only the gCYb-558 pair, and was observed only under physiological magnesium conditions. These results indicate that the U-tail contribution can differ substantially between the different gRNA/mRNA pairs. In addition, our results suggest that the efficiency of gRNA/mRNA interaction is highly dependent on thermodynamic parameters determined by the local sequences and their adopted structures surrounding the anchor-binding site.