Instruct: Given a question, retrieve relevant passages that can help answer the question.
Query: What's RNA?
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and DNA are nucleic acids, and, along with lipids, proteins and carbohydrates, constitute the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA it is more often found in nature as a single-strand folded onto itself, rather than a paired double-strand. Cellular organisms use messenger RNA (mRNA) to convey genetic information (using the nitrogenous bases of guanine, uracil, adenine, and cytosine, denoted by the letters G, U, A, and C) that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.
Small RNA are <200 nt (nucleotide) in length, and are usually non-coding RNA molecules. RNA silencing is often a function of these molecules, with the most common and well-studied example being RNA interference (RNAi), in which endogenously expressed microRNA (miRNA) or exogenously derived small interfering RNA (siRNA) induces the degradation of complementary messenger RNA. Other classes of small RNA have been identified, including piwi-interacting RNA (piRNA) and its subspecies repeat associated small interfering RNA (rasiRNA). Small RNA "is unable to induce RNAi alone, and to accomplish the task it must form the core of the RNA–protein complex termed the RNA-induced silencing complex (RISC), specifically with Argonaute protein". Also, mRNA is used in transcription.
Upon recruitment of the tri-snRNP, several RNA-RNA rearrangements precede the first catalytic step and further rearrangements occur in the catalytically active spliceosome. Several of the RNA-RNA interactions are mutually exclusive; however, it is not known what triggers these interactions, nor the order of these rearrangements. The first rearrangement is probably the displacement of U1 snRNP from the 5' splice site and formation of a U6 snRNA interaction. It is known that U1 snRNP is only weakly associated with fully formed spliceosomes, and U1 snRNP is inhibitory to the formation of a U6-5' splice site interaction on a model of substrate oligonucleotide containing a short 5' exon and 5' splice site. Binding of U2 snRNP to the branch point sequence (BPS) is one example of an RNA-RNA interaction displacing a protein-RNA interaction. Upon recruitment of U2 snRNP, the branch binding protein SF1 in the commitment complex is displaced since the binding site of U2 snRNA and SF1 are mutually exclusive events.
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.
By 1958, experiments and analysis such as the Avery–MacLeod–McCarty experiment, the Hershey–Chase experiment, the and the Meselson–Stahl experiment had shown DNA to be the molecule of genetic information. It was not known, however, how DNA directed the expression of proteins, or what role RNA had in these processes. Nirenberg teamed up with Heinrich J. Matthaei at the National Institutes of Health to answer these questions. They produced RNA composed solely of uracil, a nucleotide that only occurs in RNA. They then added this synthetic poly-uracil RNA into a cell-free extract of "Escherichia coli" which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid, the building blocks of proteins, and 19 unlabeled amino acids to the extract, varying the labeled amino acid in each sample. Only in the extract containing the radioactively labeled phenylalanine, was the resulting protein also radioactive. This implied that the genetic code for phenylalanine on RNA consisted of a repetition of uracil bases. Indeed, as we know now, it is UUU (three uracil bases in a row). This was the first step in deciphering the codons of the genetic code and the first demonstration of messenger RNA ("see Nirenberg and Matthaei experiment").
Systematic names of transferases are constructed in the form of "donor:acceptor grouptransferase." For example, methylamine:L-glutamate N-methyltransferase would be the standard naming convention for the transferase methylamine-glutamate N-methyltransferase, where methylamine is the donor, L-glutamate is the acceptor, and methyltransferase is the EC category grouping. This same action by the transferase can be illustrated as follows:
However, other accepted names are more frequently used for transferases, and are often formed as "acceptor grouptransferase" or "donor grouptransferase." For example, a DNA methyltransferase is a transferase that catalyzes the transfer of a methyl group to a DNA acceptor. In practice, many molecules are not referred to using this terminology due to more prevalent common names. For example, RNA Polymerase is the modern common name for what was formerly known as RNA nucleotidyltransferase, a kind of nucleotidyl transferase that transfers nucleotides to the 3’ end of a growing RNA strand. In the EC system of classification, the accepted name for RNA Polymerase is DNA-directed RNA polymerase.
There are also a number of RNA-dependent RNA polymerases that use RNA as their template for synthesis of a new strand of RNA. For instance, a number of RNA viruses (such as poliovirus) use this type of enzyme to replicate their genetic material.[25] Also, RNA-dependent RNA polymerase is part of the RNA interference pathway in many organisms.[26]
OTKONC are so-named because they exist between regions of 1-2 kilobases of sequence that are not predicted to contain any protein-coding genes. Such large non-coding regions are uncommon in bacteria, and it is likely that OTKONC RNAs are present in bacteria in view of protein-coding genes that reside farther away from the RNAs.
OTKONC RNAs presumably function in "trans" as small RNAs, and it is unknown what, if anything, their function has to do with the surrounding non-coding regions.
The northern blot is used to study the expression patterns of a specific type of RNA molecule as relative comparison among a set of different samples of RNA. It is essentially a combination of denaturing RNA gel electrophoresis, and a blot. In this process RNA is separated based on size and is then transferred to a membrane that is then probed with a labeled complement of a sequence of interest. The results may be visualized through a variety of ways depending on the label used; however, most result in the revelation of bands representing the sizes of the RNA detected in sample. The intensity of these bands is related to the amount of the target RNA in the samples analyzed. The procedure is commonly used to study when and how much gene expression is occurring by measuring how much of that RNA is present in different samples. It is one of the most basic tools for determining at what time, and under what conditions, certain genes are expressed in living tissues.
In humans cells, SIRT7 has only been shown to interact with two other molecules: RNA polymerase I (RNA Pol I) and upstream binding factor (UBF). SIRT7 is localized to the nucleolus and interacts with RNA Pol I. Chromatin immunoprecipitation studies demonstrate that SIRT7 localizes to rDNA, and coimmunoprecipitation shows that SIRT7 binds RNA Pol I. In addition SIRT7 interacts with UBF, a major component of the RNA Pol I initiation complex. It is not known whether or not SIRT7 is modifying RNA Pol I and/or UBF, and if so, what those modifications are.
RNA interference (RNAi) was first reported in 1995 by Guo and Kemphues, and similar pathways collectively referred to as RNA silencing were discovered in plants and fungi. The mechanism of RNA silencing began to be understood in 1998 with the experiments of Fire and colleagues demonstrating that double-stranded RNA triggered RNAi. RNA silencing pathways process long RNAs into small RNAs that direct the repression of transcription or translation of nucleic acid targets with sequence corresponding to the small RNAs. These single-stranded RNAs, referred to as guide strands, are incorporated into RNA silencing effector complexes such as the RNA-induced silencing complex (RISC). These RNA silencing effector complexes contain Argonaute family proteins.
RNA viruses can be further classified according to the sense or polarity of their RNA into negative-sense and positive-sense, or ambisense RNA viruses. Positive-sense viral RNA is similar to mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA-dependent RNA polymerase before translation. As such, purified RNA of a positive-sense virus can directly cause infection though it may be less infectious than the whole virus particle. Purified RNA of a negative-sense virus is not infectious by itself as it needs to be transcribed into positive-sense RNA; each virion can be transcribed to several positive-sense RNAs. Ambisense RNA viruses resemble negative-sense RNA viruses, except they also translate genes from the positive strand.
OLE RNA (Ornate Large Extremophilic RNA) is a conserved RNA structure present in certain bacteria. The RNA averages roughly 610 nucleotides in length. The only known RNAs that are longer than OLE RNA are ribozymes such as the group II intron and ribosomal RNAs. The exceptional length and highly conserved structure of OLE RNA prompted the hypothesis that OLE RNA could be a ribozyme, or otherwise perform an intricate biochemical task.
Microfluidic platforms such as the Agilent Bioanalyzer are useful in assessing the quality of exRNA samples. With the Agilent Bioanalyzer, a lab-on-chip technology that uses a sample of isolated RNA measures the length and quantity of RNA in the sample, and the results of the experiment can be represented as a digital electrophoresis gel image or an electropherogram. Because a diverse range of RNAs can be detected by this technology, it is an effective method for more generally determining what types of RNAs are present in exRNAs samples through using size characterization.
M. Sumper and R. Luce of Eigen's laboratory demonstrated that a mixture containing no RNA at all but only RNA bases and Qβ replicase can, under the right conditions, spontaneously generate self-replicating RNA which evolves into a form similar to Spiegelman's Monster. Note that despite the term self-replicating RNA, the RNA did not replicate itself: the Qβ enzyme is what made the RNA molecules.
Structurally, the "psaA" RNA motif consists of a somewhat complex arrangement of stems resulting from base pairing, and many stem-loops are terminated by the stable UNCG tetraloop. Most of the conserved nucleotides in the motif participate in standard Watson-Crick base pairs. However, since the precise function of "psaA" RNAs is unknown, it is also unknown what biochemical role these features play.
The "sbcD" RNA motif is a conserved RNA structure identified using bioinformatics. "sbc" RNAs are found some species of bacteria classified under the family Burkholderiaceae, and usually reside in plasmids. They are always located in what might be the 5' untranslated regions of operons that include "sbcD" genes. "sbcD" genes are involved in DNA repair.
The RNA polymerases treat the RNA genome as double stranded DNA due to the folded rod-like structure it is in. Three forms of RNA are made; circular genomic RNA, circular complementary antigenomic RNA, and a linear polyadenylated antigenomic RNA, which is the mRNA containing the open reading frame for the HDAg. Synthesis of antigenomic RNA occurs in the nucleolus, mediated by RNA Pol I, whereas synthesis of genomic RNA takes place in the nucleoplasm, mediated by RNA Pol II. HDV RNA is synthesized first as linear RNA that contains many copies of the genome. The genomic and antigenomic RNA contain a sequence of 85 nucleotides, the Hepatitis delta virus ribozyme, that acts as a ribozyme, which self-cleaves the linear RNA into monomers. These monomers are then ligated to form circular RNA.
Termite-"flg" RNAs are consistently located in what is presumed to be the 5' untranslated regions of genes that encode proteins whose functions relate to flagella. The RNAs are hypothesized to regulate these genes in an unknown mechanism.
The "Pseudomon"-Rho RNA motif refers to a conserved RNA structure that was discovered using bioinformatics. The RNAs that conform to this motif (see diagram) are found in species within the genus "Pseudomonas", as well as the related "Azotobacter vinelandii". They are consistently located in what could be the 5' untranslated regions of genes that encode the Rho factor protein, and this arrangement in bacteria suggested that "Pseudomon"-Rho RNAs might be cis-regulatory elements that regulate concentrations of the Rho protein.
The earliest work in RNA structural biology coincided, more or less, with the work being done on DNA in the early 1950s. In their seminal 1953 paper, Watson and Crick suggested that van der Waals crowding by the 2`OH group of ribose would preclude RNA from adopting a double helical structure identical to the model they proposed - what we now know as B-form DNA. This provoked questions about the three-dimensional structure of RNA: could this molecule form some type of helical structure, and if so, how? As with DNA, early structural work on RNA centered around isolation of native RNA polymers for fiber diffraction analysis. In part because of heterogeneity of the samples tested, early fiber diffraction patterns were usually ambiguous and not readily interpretable. In 1955, Marianne Grunberg-Manago and colleagues published a paper describing the enzyme polynucleotide phosphorylase, which cleaved a phosphate group from nucleotide diphosphates to catalyze their polymerization. This discovery allowed researchers to synthesize homogenous nucleotide polymers, which they then combined to produce double stranded molecules. These samples yielded the most readily interpretable fiber diffraction patterns yet obtained, suggesting an ordered, helical structure for cognate, double stranded RNA that differed from that observed in DNA. These results paved the way for a series of investigations into the various properties and propensities of RNA. Through the late 1950s and early 1960s, numerous papers were published on various topics in RNA structure, including RNA-DNA hybridization, triple stranded RNA, and even small-scale crystallography of RNA di-nucleotides - G-C, and A-U - in primitive helix-like arrangements. For a more in-depth review of the early work in RNA structural biology, see the article "The Era of RNA Awakening: Structural biology of RNA in the early years" by Alexander Rich.
According to the length of RNA chain, RNA includes small RNA and long RNA.[34] Usually, small RNAs are shorter than 200nt in length, and long RNAs are greater than 200nt long.[35] Long RNAs, also called large RNAs, mainly include long non-coding RNA (lncRNA) and mRNA. Small RNAs mainly include 5.8S ribosomal RNA (rRNA), 5S rRNA, transfer RNA (tRNA), microRNA (miRNA), small interfering RNA (siRNA), small nucleolar RNA (snoRNAs), Piwi-interacting RNA (piRNA), tRNA-derived small RNA (tsRNA)[36] and small rDNA-derived RNA (srRNA).[37]
RNA transfection is the process of deliberately introducing RNA into a living cell. RNA can be purified from cells after lysis or synthesized from free nucleotides either chemically, or enzymatically using an RNA polymerase to transcribe a DNA template. As with DNA, RNA can be delivered to cells by a variety of means including microinjection, electroporation, and lipid-mediated transfection. If the RNA encodes a protein, transfected cells may translate the RNA into the encoded protein. If the RNA is a regulatory RNA (such as a miRNA), the RNA may cause other changes in the cell (such as RNAi-mediated knockdown).
As nuclear RNA emerges from RNA polymerase, RNA transcripts are immediately covered with RNA-binding proteins that regulate every aspect of RNA metabolism and function including RNA biogenesis, maturation, transport, cellular localization and stability. All RBPs bind RNA, however they do so with different RNA-sequence specificities and affinities, which allows the RBPs to be as diverse as their targets and functions. These targets include mRNA, which codes for proteins, as well as a number of functional non-coding RNAs. NcRNAs almost always function as ribonucleoprotein complexes and not as naked RNAs. These non-coding RNAs include microRNAs, small interfering RNAs (siRNA), as well as splicesomal small nuclear RNAs (snRNA).
RNA origami is the nanoscale folding of RNA, enabling the RNA to create particular shapes to organize these molecules. It is a new method that was developed by researchers from Aarhus University and California Institute of Technology. RNA origami is synthesized by enzymes that fold RNA into particular shapes. The folding of the RNA occurs in living cells under natural conditions. RNA origami is represented as a DNA gene, which within cells can be transcribed into RNA by RNA polymerase. Many computer algorithms are present to help with RNA folding, but none can fully predict the folding of RNA of a singular sequence.