Ribonucleic acid (abbreviated as RNA) exists in biological cells, some virusesViroidThe carrier of genetic information in.RNA consists ofRibonucleotidethroughPhosphodiester bondIt condenses to form chain like molecules.A ribonucleotide molecule consists ofphosphoric acid，RiboseandBaseComposition.There are mainly four bases of RNA, namely A（adenine）、G（Guanine）、C（cytosine ）、U（Uracil）, where U (uracil) replaces T in DNA（Thymine）。The role of RNA in the body is mainly to guide protein synthesis.[1]
A human cell contains about 10pg of RNA (about 7pg of DNA).Compared with DNA, RNA has many kinds, small molecular weight and large content changes.RNA can be divided intoMessenger RNAandNon coding RNA。Non coding RNA is divided into non coding large RNA and non coding small RNA.Non coding large RNAs include ribosomal RNA and long chain non coding RNA.Non coding microRNAs include transfer RNA, ribozymeSmall RNAEtc.Small RNA (20-300nt) includes miRNA, SiRNA, piRNA, scRNA, snRNA, snoRNA, etc. Bacteria also have small RNA (50-500nt).[2]
Function and distribution of different types of RNA
name
function
existence
Messenger RNA (mRNA)
Translation template.
All creatures
Transfer RNA (tRNA)
Carries amino acids and participates in translation.
All creatures
Ribosomal RNA (rRNA)
Ribosomal components, involved in translation.
All creatures
Nuclear small RNA (snRNA)
It participates in the splicing of eukaryotic nuclear mRNA precursors.
Eukaryote
Small nucleolar RNA (snoRNA)
It is involved in the post-processing of archaea and eukaryotic rRNA precursors.
Eukaryotes and Archaea
MicroRNA (microRNA or miRNA)
It mainly inhibits the expression of specific genes at the translation level.
Most eukaryotes
Enhancer RNA (eRNA)
A class of non coding RNA transcribed in the enhancer region of eukaryotes, whose function is to regulate nearby gene expression.
Eukaryote
Small interfering RNA (siRNA)
It mainly inhibits the expression of specific genes at the translation level.
Eukaryote
Small activated RNA (saRNA)
"Target" promoters of specific genes and activate their transcription.
Some eukaryotes
PiRNA or piwi RNA
The gene silencing of inversion position is very important for embryonic development and spermatogenesis of some animals.
Germ cells of vertebrates or invertebrates
Long non coding RNA (lncRNA)
Regulate gene expression in multiple links of gene expression.
Eukaryote
7SL RNA
As a part of SRP, it is involved in protein orientation and secretion.
Eukaryotes and Archaea
7SK RNA
Inhibits transcriptional extension catalyzed by RNA polymerase II.
vertebrate
RMRP RNA
It is involved in the processing of RNA primers in the process of mitochondrial DNA replication;Participate in the post processing of rRNA;The 5 'untranslated sequence of mRNA involved in the removal of a protein that blocks cell cycle promotes the progress of cell cycle.
Eukaryote
Transfer messenger RNA (tmRNA)
It has the function of both mRNA and tRNA and participates in the rescue translation of prokaryotic mRNA without stop codon.
Bacteria
crRNA
Lock the foreign nucleic acid and guide the Cas protein to hydrolyze the foreign nucleic acid.
Most prokaryotes
tracrRNA
It binds to crRNA to guide Cas protein.
Most prokaryotes
Guide RNA (gRNA)
It participates in the editing of mitochondrial mRNA of Trypanosoma.
Some eukaryotes
Viroid
The smallest infectious pathogenic factor.
Botany
Telomerase RNA
As a template of telomerase, it is helpful for the integrity of telomere DNA.
Eukaryote
Nuclear switch or RNA switch
Regulate gene expression at the transcription or translation level.
Prokaryotes and a few lower eukaryotes
ribozyme
It catalyzes specific biochemical reactions, such as ribonuclease P and transpeptidase on ribosomes.
Prokaryotic or eukaryotic organisms and some RNA viruses
CircRNA
As competitive endogenous RNA, it participates in regulating the function of specific miRNAs in cells;It can also bind to some RNA binding proteins in cells and regulate the interaction between these proteins and other RNAs.
Mainly eukaryotes
Xist RNA
Promote the transformation of an X chromosome into a highly concentrated Barr body in mammals.
Female mammals[7]
Messenger RNA
Messenger RNA (mRNA) was first discovered in 1960protein synthesisIn the process, it is responsible for transmitting genetic information and directly guiding protein synthesis, with the following characteristics.[2]
1. The content is low, accounting for 1%~5% of the total RNA of cells.[2]
2. Various types, up to 10fiveSpecies.Differentgene expressionDifferent mRNA.[2]
3. Short life span, different mRNA guides the synthesis of different proteins, which will be degraded after completing the mission.Average of bacterial mRNAhalf lifeAbout 1.5 minutes.The half-life of vertebrate mRNA varies greatly, with an average of about 3 hours.[2]
4. The length difference of large mammalian mRNA is 5 × 10two~1×10fiveAlthough there are structural differences between nt prokaryotes and eukaryotes, their mRNA functions are the same, and they are both templates guiding protein synthesis.[2]
Transfer RNA
Transfer RNA
Transfer RNA (tRNA) is responsible for transporting amino acids and interpreting the genetic code of mRNA in the process of protein synthesis.TRNA accounts for 10%~15% of the total RNA in cells, and most of them are located in the cytoplasm.TRNA was proposed by Crick in 1955 and identified by Zamecnik and Hoagland in 1957.[2]
1. tRNA primary structure
It has the following characteristics:[2]
① It is a kind of single stranded small molecule RNA, 73~95nt long (76nt in total), with sedimentation coefficient of 4S.[2]
② Yes withRare baseThe most RNA, containing 7-15 rare bases (accounting for 15%~20% of all bases), is located in the unpaired region.[2]
③ The 5 'terminal base is often guanine.[2]
④ The 3 'end is the CCA sequence, in which the adenylate is often called A76, and its 3' - OH is the amino acid binding site.[2]
2. tRNA secondary structure
About 50% base pairs form four segments of double helix and five segments of unpaired sequence form a clover like structure.There are four arms and four rings in the structure:
① Amino acid arm.[2]
② Dihydrouracil arm (DHU arm, D arm) and Dihydrouracil ring (DHU ring, D ring), characterized by containing Dihydrouracil (DHU, D).[2]
③ Anticodon arm sumAnticode subring, characterized by the anti codon ring containing anti codon.The 5 'end of the anti codon is connected with uridine, and the 3' end is connected with uridinePurine nucleotideconnect.TΨC-arm (T-arm) and TΨC-ring（ΨRing), characterized by TΨC ring containsThymineRibonucleotideT54 pseudouridineΨ55 Cytidine acid C56.[2]
④ Extra rings 3~21nt.[2]
3. Tertiary structure of tRNA
L-shaped, with amino acid binding site at one end, anti codon ring at the other end, DHU ring and TΨAlthough the C-ring is located on both sides in the secondary structure, it is adjacent in the tertiary structure.Although the length and sequence of various tRNAs are different, their tertiary structures are similar, suggesting that tertiary structures are closely related to their functions.[2]
The ribosomes of prokaryotes and eukaryotes are composed of a large subunit and a small subunit, and both subunits are composed of rRNA and ribosomal proteins.RibosomeRibosomal subunitAnd rRNA are generally expressed by sedimentation coefficient.[2]
2. Ribosomal RNA characteristics
(1) High content, rRNA is the most abundant RNA in the cell, accounting for 80%~85% of the total RNA in the cell.[2]
(2) Long life, slow rRNA update, long life.[2]
(3) There are few species. Prokaryotes have 5S, 16S and 23s rRNAs, accounting for 66% of the ribosome mass (of which 5S and 23S rRNAs account forRibosome large subunit70%, 16S rRNARibosome small subunit60%);Eukaryotes mainly have four kinds of rRNAs: 5S, 5.8S, 18S, 28S, and a small amount of mitochondrial rRNA and chloroplast rRNA.Escherichia coli 16SrRNA has a conserved sequence ACCUCCU at the 3 'end, which can be complementary to the SD sequence in the mRNA.5 Two conserved sequences of SrRNA have also been identified:[2]
① CGAAC, which can be compared with TΨComplementary combination of GTCG of C-ring.[2]
② GCGCCGAAUGUAGU can be complementary to a segment of 23SrRNA.[2]
3. Ribosome type
There is only one kind of prokaryotesribosome，EukaryoteThere are the following types located in different parts of cells: ribosomesFree ribosomeEndoplasmic reticulum ribosome (also called attached ribosome)Mitochondrial ribosomeandChloroplast ribosome(plants).Free ribosomes and endoplasmic reticulum ribosomes are actually the same kind of ribosomes. They are larger than prokaryotic ribosomes and contain more rRNA and protein.Mitochondrial ribosomes and chloroplast ribosomes are smaller than prokaryotic ribosomes.However, the basic structure and function of these ribosomes are the same.[2]
ribozyme
When studying the post transcriptional processing of RNA, scientists found that some RNAs have catalytic activity and can catalyze RNA splicing. These RNA synthesized by living cells and playing a catalytic role are called ribozymes.The substrate of many ribozymes is also RNA, even its own, and its catalytic reaction is also specific.[2]
The clarified natural ribozymes include hammerhead ribozyme, hairpin ribozymeType I intron, type II intron, hepatitis D virus ribozymeRibonuclease P、PeptidyltransferaseEtc.How to evaluate the theoretical and practical significance of ribozyme and how to view the role of ribozyme and enzymes in the traditional sense in metabolism need further research.[2]
1. Ribozyme discovery
Ribozyme was first discovered by Cech and Altman (winners of the 1989 Nobel Prize in Chemistry).In 1967, Woese, Crick and Orgel proposed that RNA might have catalytic activity based on the complexity of its secondary structure;In 1982, Cech found that the intron of Tetrahymena tetrahymena had self splicing activity when studying the splicing of its rRNA precursor;In 1983, Altman found that MRNA in ribonuclease P was involved in the post transcriptional processing of tRNA precursors when studying bacterial tRNA precursors;In 1982, Kruger and others suggested that RNA with catalytic activity should be named "ribozyme".[2]
2. Ribozyme characteristics
The ribozymes discovered so far have the following characteristics.[2]
(1) The chemical nature of ribozyme is RNA or RNA fragment.SomeRibonucleoproteinIt also has catalytic effect, but the active center is located on its protein component and does not belong to ribozyme, such as telomerase.However, if the RNA of a ribonucleoprotein contains an active center, the RNA component is a ribozyme, such as M in the ribonuclease P moleculeoneRNA。[2]
(2) Ribozymes have relatively few kinds of substrates, most of which are self RNA or other RNA molecules, so they can be divided into two types: self catalysis and heterocatalysis.In addition, there are other substrates, for example, the substrates of peptidyltransferase are aminoacyl tRNA and peptidyl tRNA.[2]
(3) The catalytic efficiency of ribozyme is much lower than that of enzyme.[2]
(4) Ribozyme also has specificity.For example, MoneRNA only shears the extra nucleotides at the 5 'end of the RNA precursor, not the extra nucleotides and other sequences at the 3' end.[2]
(5) The reactions catalyzed by ribozyme are irreversible.[2]
(6) Mg is required for ribozyme catalyzed reaction2+，Mg3+It not only maintains the active conformation of ribozyme, but also participates in catalytic reaction.[2]
(7) Most ribozymes are extremely low in cells.[2]
3. Significance of ribozyme
① The discovery and research of ribozyme have made us further understand the physiological function of RNA, that is, it is not only the carrier of genetic information, but also the carrier of genetic informationBiocatalystIt has the functions of both DNA and protein biomacromolecules.[2]
② The discovery of ribozyme has shaken the traditional idea that all biocatalysts are proteins.[2]
③ The discovery of ribozyme is of great significance for understanding the process of life evolution. RNA may be the earliest biological macromolecule.[2]
Toad blood smear (stained with piro red methyl green dye)
90% of eukaryotic RNA is distributed in cytoplasm, and a small amount is found in mitochondria, chloroplasts and nucleoli.[3]
The prokaryotic RNA is distributed in the cytoplasm.[3]
Composition
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Ribonucleic acid
Like DNA, RNA is also composed of various nucleotides through 3 ′, 5 ′-Phosphodiester bondConnectedPolynucleotideChain, but there are a series of differences with DNA.[4]
1. In terms of chemical composition, RNA contains ribose but not deoxyribose.It contains uracil but not thymidine.The exception is that each tRNA molecule contains one thymine, which is methylated by uracil after RNA chain synthesis. In addition, as mentioned earlier, a few DNA contains a small amount of ribose, but these individual exceptions cannot deny the difference in composition of the two types of nucleic acids.[4]
2. Although the concept of RNA primary structure is the same as that of DNA, its basic structural unit is ribonucleotide, notDeoxyribonucleotide。In addition, some RNAs have special nucleotide sequences at the A5 'or 3' ends, and the RNA primary structure is not as complex as DNA.[4]
3. Most RNAs are single stranded molecules, which can fold themselves to form hairpin like structures with localDouble helix structureThis is the common feature of various RAN spatial structures.RNA local double helix structurecomplementary base pairing The rule is A versus U and G versus C.Since the base pairing cannot be fully formed inside the RNA molecule, the ratio of base to gram molecule A is not equal to U, and G is not equal to C. There is no Chargaff rule of DNA base ratio.[4]
Interference mechanism
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In 1998, two American scientists Andrew Farr and Craig Mello jointly published a paper on discovering RNA interference mechanism in Nature, which was called "one of the most exciting discoveries in molecular biology in recent years" by their peers.[5]
Andrew Farr was born in 1959 in Santa Clara County, California, the United StatesUniversity of California, BerkeleyI majored in mathematics and got my degree in only three years.In 1983, he received a doctor's degree in biology from Massachusetts Institute of Technology.He gradually became interested in genetics, which involves the mysteries of life, and regarded it as his lifelong academic pursuit.[5]
Craig Mello was born in 1960. His father was a paleontologist. When Mello was a child, he often followed his father to search for fossils in the western United States.[5]
In high school, Mello's interest gradually shifted to genetic engineering.At that time, scientists cloned the human insulin gene and transferred its DNA（Deoxyribonucleic acid）Put it into bacteria, so that you can synthesize unlimited insulin.This achievement has brought good news to millions of diabetic patients around the world."The idea that scientific research can really affect human health aroused my interest," Mello recalled[5]
In 1998, while working at the Carnegie Institution in the United States, Farr and Melo cooperated to discoverRNA interferenceMechanism.[5]
Andrew Farr said: "Craig and I are working to study why some genes stop working. We tried to control them, and we found something that can effectively stop them. These genes can't tell you what they can do, so if you can stop them, you can start to understand what they can do.However, it was a Chinese scholar who first discovered the RNA phenomenon. Unfortunately, he did not further understand why. "[5]
What they found was a key mechanism for controlling the flow of genetic information.The human genome sends instructions for protein production from the DNA in the nucleus to the protein synthesis mechanism, and these instructions are transmitted through mRNA.They found a way to degrade mRNA with specific genesRNA interference phenomenonMedium,Double stranded RNAIt inhibits gene expression in a very specific way.This technology is used in laboratories around the world to determine which genes play an important role in various diseases.[5]
RNA interference exists in plants, animals and humans, which is of great significance for the management of gene expression, participation in the protection of virus infection, and control of active genes.RNA interference is a biological process in which double stranded RNA inhibits gene expression in a very clear way.Since its discovery in 1998, RNA interference has emerged as a powerful "gene silencing" technology.RNA interference, as a research method to study gene operation, has been widely used in basic science, and it may produce more newer therapeutic methods in the future.Scientists believe that,RNA interference technologyIt is not only a powerful tool for studying gene function. In the near future, this technology may be used to directly silence pathogenic genes from the source to treat cancer and even AIDS. It will also have great potential in agriculture.[5]
function
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mRNA
MRNA contains four nucleotides, A, U, G, and C, and every three nucleotides are linked to form a triplet, that is, a code, representing the information of an amino acid. Therefore, 43=64 different codes can be formed according to the rules of permutation and combination in mathematics.According to the experimental results, the corresponding relationship between 64 codes and amino acids is as follows.[6]
Correspondence between mRNA code and amino acid
Among 64 codes, 61 codes represent various amino acids respectively.For each amino acid, there is only one code for those with less amino acids, and 6 for those with more amino acids, but most of them are 2 and 4.In addition, the three codes of UAA, UAG and UGA are the termination signals of peptide chain synthesis and do not represent any amino acids.In eukaryotes, AUG is bothmethionineIt is also the starting signal of peptide chain synthesis;In prokaryotes, GUG (the code of valine in eukaryotes) and AUG are both the code of formylmethionine and the starting phase number of peptide chain synthesis.It can be seen that except GUG, all codes can be applied from bacteria to higher organisms, which provides strong evidence for the theory of common origin of organisms.[6]
It must be pointed out that: ① in the whole molecule of mRNA, from the start signal to the end signal, the triplet of its code is continuous, and there is no gap between the code and the nucleotide; ②The starting signal AUG is not the start (5 ′ end) of mRNA, but can be separated from 5 ′ end by several nucleotides;Moreover, the termination signal was not at the 3 'end of mRNA.[6]
tRNA
There are many kinds of tRNAs as "transportation tools", and 20 amino acids in the body have their own unique tRNAs, so there are no less than 20 kinds of tRNAs.TRNA can bind to specific amino acids under the action of ATP supplying energy and enzymes.Each tRNA has an "anti code" composed of three nucleotides.This anti code can be paired with the corresponding code on the mRNA according to the principle of base pairing, and can only be matched when the anti code corresponds to the code on the mRNA, otherwise it will be "out of place".So when translating, each tRNA with different amino acids can accuratelyMRNA moleculeIn order to ensure that the amino acids can be arranged in a certain order, they are in accordance with the classic code.[6]
The anti code on tRNA should of course be able to recognize the corresponding and complementary code on mRNA and pair with it.However, when using purified tRNA for experiments, we found that one tRNA can recognize several codes.For example, alanine tRNA, whose anti code is IGC (5 ′>3 ′), can recognize three codes.[6]
rRNA
RRNA and a variety of protein molecules together constitute ribosomes.The ribosome acts as an "assembly machine", which can facilitate the condensation of amino acyl groups carried by tRNA into peptides.The ribosome attaches to the mRNA and moves along the start signal of the mRNA long chain to the end signal.The specific role of rRNA in protein biosynthesis is unclear.[6]
