Instruct: Given a question, retrieve documents that can help answer the question.
Query: Is there any proof of RNA?
The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence of this stage.
On the leading strand, DNA polymerase can make a complementary DNA strand without any difficulty because it reads the template strand from 3' to 5'. However, there is a problem going in the other direction on the lagging strand. To counter this, short sequences of RNA acting as primers attach to the lagging strand a short distance ahead of where the initiation site was. The DNA polymerase can start replication at that point and go to the end of the initiation site. This causes the formation of Okazaki fragments. More RNA primers attach further on the DNA strand and DNA polymerase comes along and continues to make a new DNA strand.Eventually, the last RNA primer attaches, and DNA polymerase, RNA nuclease, and DNA ligase come along to convert the RNA (of the primers) to DNA and to seal the gaps in between the Okazaki fragments. But, in order to change RNA to DNA, there must be another DNA strand in front of the RNA primer. This happens at all the sites of the lagging strand, but it does not happen at the end where the last RNA primer is attached. Ultimately, that RNA is destroyed by enzymes that degrade any RNA left on the DNA. Thus, a section of the telomere is lost during each cycle of replication at the 5' end of the lagging strand's daughter.
Transcription fidelity is achieved through multiple mechanisms. RNA polymerases select correct nucleoside triphosphate (NTP) substrate to prevent transcription errors. Only the NTP which correctly base pairs with the coding base in the DNA is admitted to the active center. RNA polymerase performs two known proof reading functions to detect and remove misincorporated nucleotides: pyrophosphorylytic editing and hydrolytic editing. The former removes the incorrectly inserted ribonucleotide by a simple reversal of the polymerization reaction, while the latter involves backtracking of the polymerase and cleaving of a segment of error-containing RNA product. Elongation factor TFIIS stimulates an inherent ribonuclease activity in the polymerase, allowing the removal of misincorporated bases through limited local RNA degradation. Note that all reactions (phosphodiester bond synthesis, pyrophosphorolysis, phosphodiester bond hydrolysis) are performed by RNA polymerase by using a single active center.
Since Cech's and Altman's discovery, other investigators have discovered other examples of self-cleaving RNA or catalytic RNA molecules. Many ribozymes have either a hairpin – or hammerhead – shaped active center and a unique secondary structure that allows them to cleave other RNA molecules at specific sequences. It is now possible to make ribozymes that will specifically cleave any RNA molecule. These RNA catalysts may have pharmaceutical applications. For example, a ribozyme has been designed to cleave the RNA of HIV. If such a ribozyme were made by a cell, all incoming virus particles would have their RNA genome cleaved by the ribozyme, which would prevent infection.
The IMES-1 RNA motif is a conserved RNA structure that was identified in marine environmental sequences by two studies based on metagenomics and bioinformatics, the first analyzing metatranscriptome (RNA) data and the second using metagenome (DNA) data. These RNAs are present in environmental sequences, and as of 2009 are not known to be present in any cultivated species. However, the species that use these RNAs are most closely related to known alphaproteobacteria and gammaproteobacteria. IMES-1 RNAs make up a significant portion of marine RNA transcripts and are exceptionally abundant in that over five times as many IMES-1 RNAs were found as ribosomes in RNAs sampled from the Pacific Ocean. Only two bacterial RNAs are known (6S RNA and transfer RNA) to be more highly transcribed than ribosomes. IMES-1 RNAs were also detected in abundance in Block Island Sound in the Atlantic Ocean.
The IMES-2 RNA motif is a conserved RNA structure that was identified by a study based on metagenomics and bioinformatics, and the underlying RNA sequences were identified independently by a similar earlier study. These RNAs are present in environmental sequences, and when discovered were not known to be present in any cultivated species. However, an IMES-2 RNA has been detected in alphaproteobacterium HIMB114, which is classified in the SAR11 clade of marine bacteria. This finding fits with earlier predictions that species that use IMES-2 RNAs are most closely related to alphaproteobacteria. IMES-2 RNAs are exceptionally abundant, as twice as many IMES-2 RNAs were found as ribosomes in RNAs sampled from the Pacific Ocean. Only two bacterial RNAs are known (6S RNA and transfer RNA) to be more highly transcribed than ribosomes.
-RNA aptamers have been obtained for the chemokines CCL2 and CXCL12, the complement components C5a and ghrelin. They are currently in preclinical or clinical development. Proof-of-concept for an anti-CCL2/MCP-1 -RNA aptamers has recently been demonstrated in diabetic nephropathy patients. They can also be used as diagnostic agents.
Like DNA, RNA can carry genetic information. RNA viruses have genomes composed of RNA that encodes a number of proteins. The viral genome is replicated by some of those proteins, while other proteins protect the genome as the virus particle moves to a new host cell. Viroids are another group of pathogens, but they consist only of RNA, do not encode any protein and are replicated by a host plant cell's polymerase.[58]
The TDP-43 protein, coded for by the "TARDBP" gene, is responsible for regulation of RNA expression. The discovery of mutations in the TARDBP gene, in relation to ALS, was the first proof that RNA processing defects lead to protein inclusions typical in RNA, and contribute to the pathogenesis of the disease. Other mutations that have been shown to be associated with ALS from GWAS include ATXN2, Nek1 and TBK1.
The following units were based at RNAS Inskip:
The runway was demolished in the 1970s. The concrete from it was used to help build the M55 motorway, from which the aerials can be clearly seen. Today only the smaller taxiways exist as proof of the airfield's former existence.
Transgenic crops have been made to express dsRNA, carefully chosen to silence crucial genes in target pests. These dsRNAs are designed to affect only insects that express specific gene sequences. As a proof of principle, in 2009 a study showed RNAs that could kill any one of four fruit fly species while not harming the other three.
In the 1980s Thomas Cech, at the University of Colorado at Boulder, was studying the excision of introns in a ribosomal RNA gene in "Tetrahymena thermophila". While trying to purify the enzyme responsible for the splicing reaction, he found that the intron could be spliced out in the absence of any added cell extract. As much as they tried, Cech and his colleagues could not identify any protein associated with the splicing reaction. After much work, Cech proposed that the intron sequence portion of the RNA could break and reform phosphodiester bonds. At about the same time, Sidney Altman, a professor at Yale University, was studying the way tRNA molecules are processed in the cell when he and his colleagues isolated an enzyme called RNase-P, which is responsible for conversion of a precursor tRNA into the active tRNA. Much to their surprise, they found that RNase-P contained RNA in addition to protein and that RNA was an essential component of the active enzyme. This was such a foreign idea that they had difficulty publishing their findings. The following year, Altman demonstrated that RNA can act as a catalyst by showing that the RNase-P RNA subunit could catalyze the cleavage of precursor tRNA into active tRNA in the absence of any protein component.
In eukaryotes, the transcription is performed by three different RNA polymerase, RNA pol I for ribosomal RNAs (rRNAs), RNA polymerase II for messenger RNAs (mRNAs) and some small regulatory RNAs, and the RNA polymeerase III for small RNAs such as transfer RNAs (tRNAs). The process of positioning of the RNA polymerase II and the transcriptional machinery require the recognition of a region known as "core promoter". The elements that could be found in the core promoter include the TATA element, the TFIIB recognition element (BRE), the initiatior (Inr), and the downstream core promoter element (DPE). Promoters in eukaryotes contain one or more of these core promotes elements (but any of them are absolutely essential for promoter function), these elements are binding sites for subunits of the transcriptional machinery and are involve in the initiation of the transcription, but also they have some specific enhancer functions. In addition, the promoter activity in eukaryotes include some complexities in the way of how they integrate signals from distal factors with the core promoter.
The fact that the RNA structure is typically found in plasmids suggests that it might be involved in the regulation plasmid copy number by a "cis"-antisense mechanism in a manner similar to that of R1162-like plasmid antisense RNA. However, the "Bacillus"-plasmid RNA motif does not appear to be homologous to any such known RNA.
The COG2908 RNA motif is a conserved RNA structure that was discovered by bioinformatics.
COG2908 motif RNAs are found in genomic sequences extracted from fresh water environments. They have not, as of 2018, been detected in any classified organism.
DNA-directed RNA interference (ddRNAi) is a gene-silencing technique that utilizes DNA constructs to activate an animal cell’s endogenous RNA interference (RNAi) pathways. DNA constructs are designed to express self-complementary double-stranded RNAs, typically short-hairpin RNAs (shRNA), that once processed bring about silencing of a target gene or genes. Any RNA, including endogenous mRNAs or viral RNAs, can be silenced by designing constructs to express double-stranded RNA complementary to the desired mRNA target.
The Ocean-V RNA motif is a conserved RNA structure discovered using bioinformatics. Only a few Ocean-V RNA sequences have been detected, all in sequences derived from DNA that was extracted from uncultivated bacteria found in ocean water. As of 2010, no Ocean-V RNA has been detected in any known, cultivated organism.
RNases are ubiquitous and can often contaminate and subsequently degrade RNA samples in the laboratory, so RNA integrity can very easily be compromised, leading to a number of laboratory techniques designed to eliminate their impact. However, these methods are not fool-proof, and so samples can still be degraded, necessitating a method of measuring RNA integrity to ensure the trustworthiness and reproducibility of molecular assays, as RNA integrity is critical for proper results in gene expression studies, such as microarray analysis, Northern blots, or quantitative real-time PCR (qPCR). RNA that has been degraded has a direct impact on calculated expression levels, often leading to significantly decreased apparent expression.
RNAs that were identified in environmental sequence samples include the IMES-1, IMES-3, IMES-4, Whalefall-1, "potC", Termite-"flg" and Gut-1 RNA motifs. These RNA structures have not been detected in the genome of any known species. The IMES-2 RNA motif, GOLLD RNA motif and manA RNA motif were discovered using environmental DNA or RNA sequence samples, and are present in a small number of known species. Additional non-coding RNAs are predicted in marine environments, although no specific conserved secondary structures have been published for these other candidates. Other conserved RNA structures were originally detected using environmental sequence data, e.g., the glnA RNA motif, but were subsequently detected in numerous cultivated species of bacteria.
The "queA" RNA motif is a conserved RNA structure that was discovered by bioinformatics.
"queA" motif RNAs have not yet (as of 2018) been found in any classified organism; they are known from metagenomic sequences.
The IMES-4 RNA motif is a conserved RNA structure that was identified in marine environmental sequences by metagenomics and bioinformatics. These RNAs are present in environmental sequences, and as of 2009 are not known to be present in any cultivated species. IMES-4 RNAs are fairly abundant in comparison to ribosomes in RNAs sampled from the Pacific Ocean.
RNA spike-ins can be synthesized by any means of creating RNA synthetically, or by using cells to transcribe DNA to RNA "in vivo" (in cells). RNA can be produced "in vitro" (cell free) using RNA polymerase and DNA with the desired sequence. Large scale biotech manufacturers produce RNA synthetically via high-throughput techniques and provide solutions of RNA spike-ins at predetermined concentration. Bacteria containing DNA (usually on plasmids) for transcription to spike-ins are also commercially available. The purified RNA can be stored long-term in a buffered solution at low temperature.
The IMES-3 RNA motif is a conserved RNA structure that was identified based on metagenomics and bioinformatics, and the underlying RNA sequences were identified independently by an earlier study. These RNAs are present in environmental sequences, and as of 2009 are not known to be present in any cultivated species. IMES-3 RNAs are abundant in comparison to ribosomes in RNAs sampled from the Pacific Ocean.
The Whalefall-1 RNA motif (also called wf-1) refers to a conserved RNA structure that was discovered using bioinformatics. Structurally, the motif consists of two stem-loops (see diagram), the second of which is often terminated by a CUUG tetraloop, which is an energetically favorable RNA sequence. Whalefall-1 RNAs are found only in DNA extracted from uncultivated bacteria found on whale fall, i.e., a whale carcass. As of 2010, Whalefall-1 RNAs have not been detected in any known, cultivated species of bacteria, and are thus one of several RNAs present in environmental samples.
Subsequent studies identified novel RNAs exclusively using sequences extracted from environmental samples. 
The first study determined the sequences of RNAs directly extracted from microbial biomass in the Pacific Ocean. The researches found that a large fraction of the total extracted RNA molecules did not appear to code for protein, but instead appear to conserve consistent RNA secondary structures. A number of these were shown to belong to known small RNA sequence families, including riboswitches. A larger fraction of these microbial small RNAs appeared to represent novel, non-coding small RNAs, not yet described in any databases.
A second study used sequences of DNA extracted from various environments, and inferred the presence of conserved RNA secondary structures among some of these sequences. Both studies identified RNAs that were not present in then-available genome sequences of any known organisms, and determined that some of the RNAs were remarkably abundant. In fact, two of the RNA classes (the IMES-1 RNA motif and IMES-2 RNA motif) exceeded ribosomes in copy number, which is extremely unusual among RNAs in bacteria. IMES-1 RNAs were also determined to be highly abundant near the shore in the Atlantic Ocean using different techniques.