Messenger ribonucleic acid (mRNA) is a molecule of RNA encoding a chemical "blueprint" for a protein product. Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Transcription is the synthesis of RNA under the direction of DNA Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Protein synthesis is the creation of proteins using DNA and' RNA'. Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein. Translation is the first stage of Protein biosynthesis (part of the overall process of Gene expression) In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this In mRNA as in DNA, genetic information is encoded in the sequence of four nucleotides arranged into codons of three bases each. Nucleotides are Organic compounds that consist of three joined structures a nitrogenous base a Sugar, and a Phosphate group The genetic code is the set of rules by which information encoded in genetic material ( DNA or RNA sequences is translated into Proteins Each codon encodes for a specific amino acid, except the stop codons that terminate protein synthesis. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this In the Genetic code, a stop codon (or termination codon) is a Nucleotide triplet within Messenger RNA that signals a termination of translation This process requires two other types of RNA: transfer RNA (tRNA) mediates recognition of the codon and provides the corresponding amino acid, while ribosomal RNA (rRNA) is the central component of the ribosome's protein manufacturing machinery. Transfer RNA (abbreviated tRNA) is a small RNA (usually about 74-95 nucleotides that transfers a specific Amino acid to a growing polypeptide chain at Ribosomal RNA ( rRNA) is the central component of the Ribosome, the protein manufacturing machinery of all living cells.
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Messenger RNA (mRNA)
The brief existence of an mRNA molecule begins with transcription and ultimately ends in degradation. During its life, an mRNA molecule may also be processed, edited, and transported prior to translation. Eukaryotic mRNA molecules often require extensive processing and transport, while prokaryotic molecules do not. Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex The prokaryotes (proʊˈkærioʊts singular prokaryote /proʊˈkæriət/ are a group of Organisms that lack a Cell nucleus (= karyon or any other
Transcription
During transcription, RNA polymerase makes a copy of a gene from the DNA to mRNA as needed. Transcription is the synthesis of RNA under the direction of DNA RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. This process is similar in eukaryotes and prokaryotes. One notable difference, however, is that eukaryotic RNA polymerase associates with mRNA processing enzymes during transcription so that processing can proceed quickly after the start of transcription. The short-lived, unprocessed or partially processed, product is termed pre-mRNA; once completely processed, it is termed mature mRNA. Precursor mRNA ( pre-mRNA) also termed heterogeneous nuclear RNA ( hnRNA) is an immature single strand of messenger ribonucleic acid ( MRNA Mature Messenger RNA, often abbreviated as mature mRNA is a Eukaryotic RNA transcript that has been spliced and processed and is ready
Eukaryotic pre-mRNA processing
Processing of mRNA differs greatly among eukaryotes, bacteria and archea. Post-transcriptional modification is a process in Cell biology by which in Eukaryotic cells, primary transcript RNA is converted into mature Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Non-eukaryotic mRNA is essentially mature upon transcription and requires no processing, except in rare cases. Eukaryotic pre-mRNA, however, requires extensive processing.
5' cap addition
A 5' cap (also termed an RNA cap, an RNA 7-methylguanosine cap or an RNA m7G cap) is a modified guanine nucleotide that has been added to the "front" or 5' end of a eukaryotic messenger RNA shortly after the start of transcription. The 5' cap is a specially altered Nucleotide end to the 5' end of Precursor messenger RNA and some other primary RNA transcripts as found in Eukaryotes Directionality, in Molecular biology, refers to the end-to-end chemical orientation of a single strand of Nucleic acid. The 5' cap consists of a terminal 7-methylguanosine residue which is linked through a 5'-5'-triphosphate bond to the first transcribed nucleotide. Its presence is critical for recognition by the ribosome and protection from RNases. Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that Ribonuclease, abbreviated commonly as RNase, is a Nuclease that catalyzes the degradation of RNA into smaller components
Cap addition is coupled to transcription, and occurs co-transcriptionally, such that each influences the other. Shortly after the start of transcription, the 5' end of the mRNA being synthesized is bound by a cap-synthesizing complex associated with RNA polymerase. RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. This enzymatic complex catalyzes the chemical reactions that are required for mRNA capping. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Catalysis is the process in which the rate of a Chemical reaction is increased by means of a Chemical substance known as a catalyst Synthesis proceeds as a multi-step biochemical reaction. Biochemistry is the study of the chemical processes in living Organisms It deals with the Structure and function of cellular components such as
Splicing
Splicing is the process by which pre-mRNA is modified to remove certain stretches of non-coding sequences called introns; the stretches that remain include protein-coding sequences and are called exons. In Molecular biology, splicing is a modification of an RNA after transcription, in which Introns are removed and Exons are joined Introns, derived from the term "intragenic regions" and also called intervening sequence (IVS are DNA regions in a Gene that are not translated into An exon is a Nucleic acid sequence that is represented in the mature form of an RNA molecule after a portions of a precursor RNA Introns have been Sometimes pre-mRNA messages may be spliced in several different ways, allowing a single gene to encode multiple proteins. This process is called alternative splicing. Alternative splicing is the RNA splicing variation mechanism in which the Exons of the primary gene transcript the Pre-mRNA, are separated and reconnected Splicing is usually performed by an RNA-protein complex called the spliceosome, but some RNA molecules are also capable of catalyzing their own splicing (see ribozymes). A spliceosome is a complex of specialized RNA and Protein subunits that removes Introns from a transcribed pre- mRNA ( HnRNA A ribozyme (from ribo nucleic acid en' zyme', also called RNA Enzyme or catalytic RNA is an RNA Molecule that catalyzes
Editing
In some instances, an mRNA will be edited, changing the nucleotide composition of that mRNA. The term RNA editing describes those molecular processes in which the information content in an RNA molecule is altered through a chemical change in the base makeup An example in humans is the apolipoprotein B mRNA, which is edited in some tissues, but not others. The editing creates an early stop codon, which upon translation, produces a shorter protein.
Polyadenylation
Polyadenylation is the covalent linkage of a polyadenylyl moiety to a messenger RNA molecule. Polyadenylation is the synthesis of a poly(A tail a stretch of RNA where all the bases are Adenines at the end of an RNA molecule In eukaryotic organisms, most messenger RNA (mRNA) molecules are polyadenylated at the 3' end. The poly(A) tail and the protein bound to it aid in protecting mRNA from degradation by exonucleases. Messenger ribonucleic acid ( mRNA) is a molecule of RNA encoding a chemical "blueprint" for a Protein product Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, and translation. mRNA can also be polyadenylated in prokaryotic organisms, where poly(A) tails act to facilitate, rather than impede, exonucleolytic degradation.
Polyadenylation occurs during and immediately after transcription of DNA into RNA. After transcription has been terminated, the mRNA chain is cleaved through the action of an endonuclease complex associated with RNA polymerase. The cleavage site is characterized by the presence of the base sequence AAUAAA near the cleavage site. After the mRNA has been cleaved, 80 to 250 adenosine residues are added to the free 3' end at the cleavage site. This reaction is catalyzed by polyadenylate polymerase.
Transport
Another difference between eukaryotes and prokaryotes is mRNA transport. Because eukaryotic transcription and translation is compartmentally separated, eukaryotic mRNAs must be exported from the nucleus to the cytoplasm. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. Mature mRNAs are recognized by their processed modifications and then exported through the nuclear pore. Nuclear pores are large Protein complexes that cross the Nuclear envelope, which is the double membrane surrounding the eukaryotic
Translation
Because prokaryotic mRNA does not need to be processed or transported, translation by the ribosome can begin immediately after the end of transcription. Translation is the first stage of Protein biosynthesis (part of the overall process of Gene expression) Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that Therefore, it can be said that prokaryotic translation is coupled to transcription and occurs co-transcriptionally.
Eukaryotic mRNA that has been processed and transported to the cytoplasm (i. e. mature mRNA) can then be translated by the ribosome. Translation may occur at ribosomes free-floating in the cytoplasm, or directed to the endoplasmic reticulum by the signal recognition particle. Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that The endoplasmic reticulum (Greek endo = "within" (prefix plásma = "formed entity" Latin reticulum = "little net" or ER, is an Organelle The signal recognition particle (SRP is a Ribonucleoprotein ( Protein - RNA complex that recognizes and transports specific proteins to the Endoplasmic Therefore, unlike prokaryotes, eukaryotic translation is not directly coupled to transcription.
Degradation
After a certain amount of time, the message is degraded by RNases. Ribonuclease, abbreviated commonly as RNase, is a Nuclease that catalyzes the degradation of RNA into smaller components The limited lifetime of mRNA enables a cell to alter protein synthesis rapidly in response to its changing needs.
Different mRNAs within the same cell have distinct lifetimes (stabilities). In bacterial cells, individual mRNAs can survive from seconds to more than an hour; in mammalian cells, mRNA lifetimes range from several minutes to days. The greater the stability of an mRNA, the more protein may be produced from that mRNA. The presence of AU-rich elements in some mammalian mRNAs tends to destabilize those transcripts through the action of cellular proteins that bind these motifs. An AU-rich element or "ARE" is a region with frequent A and U bases in a MRNA that targets it for degradation Rapid mRNA degradation via AU-rich elements is a critical mechanism for preventing the overproduction of potent cytokines such as tumor necrosis factor (TNF) and granulocyte-macrophage colony stimulating factor (GM-CSF). An AU-rich element or "ARE" is a region with frequent A and U bases in a MRNA that targets it for degradation [1] Base pairing with a small interfering RNA (siRNA) or microRNA (miRNA) can also accelerate mRNA degradation. Small interfering RNA ( siRNA) sometimes known as short interfering RNA or silencing RNA, is a class of 20-25 Nucleotide -long double-stranded In Genetics, microRNAs ( miRNA) are single-stranded RNA molecules of about 21–23 Nucleotides in length which regulate Gene expression
mRNA structure
5' cap
The 5' cap is a modified guanine nucleotide added to the "front" (5' end) of the pre-mRNA using a 5',5-Triphosphate linkage. The 5' cap is a specially altered Nucleotide end to the 5' end of Precursor messenger RNA and some other primary RNA transcripts as found in Eukaryotes Directionality, in Molecular biology, refers to the end-to-end chemical orientation of a single strand of Nucleic acid. This modification is critical for recognition and proper attachment of mRNA to the ribosome, as well as protection from 5' exonucleases. It may also be important for other essential processes, such as splicing and transport.
Coding regions
Coding regions are composed of codons, which are decoded and translated into one (mostly eukaryotes) or several (mostly prokaryotes) proteins by the ribosome. The coding region of a Gene is the portion of DNA or RNA that is transcribed into another RNA, such as a messenger RNA The genetic code is the set of rules by which information encoded in genetic material ( DNA or RNA sequences is translated into Proteins Coding regions begin with the start codon and end with the one of three possible stop codons. ATG and AUG denote sequences of DNA and RNA respectively that are the Start codon or initiation Codon encoding the Amino acid In the Genetic code, a stop codon (or termination codon) is a Nucleotide triplet within Messenger RNA that signals a termination of translation In addition to protein-coding, portions of coding regions may also serve as regulatory sequences in the pre-mRNA as exonic splicing enhancers or exonic splicing silencers. Precursor mRNA ( pre-mRNA) also termed heterogeneous nuclear RNA ( hnRNA) is an immature single strand of messenger ribonucleic acid ( MRNA An exonic splicing enhancer (ESE is a DNA Sequence motif consisting of 6 bases within an Exon that directs or enhances accurate splicing of hetero-nuclear An exonic splicing silencer (ESS is a small region of an Exon that inhibits or silences splicing of the Pre-mRNA. Start codons are indicated by a AUG triplet. Stop codons are indicated by a UAA, UAG, or UGA.
Untranslated regions
Untranslated regions (UTRs) are sections of the mRNA before the start codon and after the stop codon that are not translated, termed the five prime untranslated region (5' UTR) and three prime untranslated region (3' UTR), respectively. The five prime untranslated region ( 5' UTR) also known as the leader sequence, is a particular section of Messenger RNA (mRNA and the DNA that codes for The three prime untranslated region (3' UTR is a particular section of Messenger RNA (mRNA The five prime untranslated region ( 5' UTR) also known as the leader sequence, is a particular section of Messenger RNA (mRNA and the DNA that codes for The three prime untranslated region (3' UTR is a particular section of Messenger RNA (mRNA These regions are transcribed with the coding region and thus are exonic as they are present in the mature mRNA. An exon is a Nucleic acid sequence that is represented in the mature form of an RNA molecule after a portions of a precursor RNA Introns have been Several roles in gene expression have been attributed to the untranslated regions, including mRNA stability, mRNA localization, and translational efficiency. Translational efficiency, in the context of cell biology is the rate of MRNA translation into Proteins within cells The ability of a UTR to perform these functions depends on the sequence of the UTR and can differ between mRNAs.
The stability of mRNAs may be controlled by the 5' UTR and/or 3' UTR due to varying affinity for RNA degrading enzymes called ribonucleases and for ancillary proteins that can promote or inhibit RNA degradation. Ribonuclease, abbreviated commonly as RNase, is a Nuclease that catalyzes the degradation of RNA into smaller components
Translational efficiency, including sometimes the complete inhibition of translation, can be controlled by UTRs. Proteins that bind to either the 3' or 5' UTR may affect translation by influencing the ribosome's ability to bind to the mRNA. MicroRNAs bound to the 3' UTR also may affect translational efficiency or mRNA stability. In Genetics, microRNAs ( miRNA) are single-stranded RNA molecules of about 21–23 Nucleotides in length which regulate Gene expression The three prime untranslated region (3' UTR is a particular section of Messenger RNA (mRNA
Cytoplasmic localization of mRNA is thought to be a function of the 3' UTR. Proteins that are needed in a particular region of the cell can actually be translated there; in such a case, the 3' UTR may contain sequences that allow the transcript to be localized to this region for translation.
Some of the elements contained in untranslated regions form a characteristic secondary structure when transcribed into RNA. In Biochemistry and Structural biology, secondary structure is the general three-dimensional form of local segments of Biopolymers such as These structural mRNA elements are involved in regulating the mRNA. Some, such as the SECIS element, are targets for proteins to bind. In Biology, the SECIS element (SECIS se leno' c' ysteine i nsertion s equence) is an RNA element around 60 One class of mRNA element, the riboswitches, directly bind small molecules, changing their fold to modify levels of transcription or translation. In Molecular biology, a riboswitch is a part of an MRNA molecule that can directly bind a small target molecule, and whose binding of the target affects In these cases, the mRNA regulates itself.
3' poly(A) tail
The 3' poly(A) tail is a long sequence of adenine nucleotides (often several hundred) added to the "tail" or 3' end of the pre-mRNA through the action of an enzyme, polyadenylate polymerase. Polyadenylation is the synthesis of a poly(A tail a stretch of RNA where all the bases are Adenines at the end of an RNA molecule Adenine is a Purine with a variety of roles in Biochemistry including Cellular respiration, in the form of both the energy-rich Adenosine Directionality, in Molecular biology, refers to the end-to-end chemical orientation of a single strand of Nucleic acid. In higher eukaryotes, the poly(A) tail is added onto transcripts that contain a specific sequence, the AAUAAA signal. The importance of the AAUAAA signal is demonstrated by a mutation in the human alpha 2-globin gene that changes the original sequence AATAAA into AATAAG, which can lead to hemoglobin deficiencies. [2]
Monocistronic versus polycistronic mRNA
An mRNA molecule is said to be monocistronic when it contains the genetic information to translate only a single protein. Translation is the first stage of Protein biosynthesis (part of the overall process of Gene expression) Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl This is the case for most of the eukaryotic mRNAs[3]. Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex On the other hand, polycistronic mRNA carries the information of several proteins, which are translated into several proteins. Most of the mRNA found in bacteria and archea are polycistronic[3]. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Dicistronic is the term used to describe a mRNA that encodes only two proteins. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl
Anti-sense RNA
During transcription, double stranded DNA produces mRNA corresponding to the sense strand. Anti-sense RNA is an RNA complementary in sequence to one or more mRNAs. In some organisms, the presence of an anti-sense mRNA can inhibit gene expression by base-pairing with the specific mRNAs. Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such In biochemical research, this effect has been used to study gene function, by simply shutting down the studied gene by adding its anti-sense mRNA transcript. Biochemistry is the study of the chemical processes in living Organisms It deals with the Structure and function of cellular components such as Such studies have been done on the worm Caenorhabditis elegans and the bacterium Escherichia coli. A worm is a common name given to a diverse group of invertebrate animals that have a long soft body and no legs Caenorhabditis elegans (ˌsiːnoʊræbˈdaɪtɪs ˈɛlɪgænz is a free-living Nematode (roundworm about 1 mm in length which The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have This plays a part in RNA interference and RNA transcription. RNA interference ( RNAi) is a mechanism that inhibits Gene expression at the stage of translation or by hindering the transcription of specific
See also
References
- ^ Shaw G, Kamen R (August 1986). Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units In Genetics, microRNAs ( miRNA) are single-stranded RNA molecules of about 21–23 Nucleotides in length which regulate Gene expression A non-coding RNA ( ncRNA) is any RNA molecule that is not translated into a Protein. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Hubert Chantrenne (born 1918 is a Belgian scientist and one of the pioneers of Molecular biology at the Université Libre de Bruxelles. "A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation". Cell 46 (5): 659–67. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 3488815.
- ^ Higgs DR, Goodbourn SE, Lamb J, Clegg JB, Weatherall DJ, Proudfoot NJ. (1983). "α-thalassaemia caused by a polyadenylation signal mutation". Nature 306 (5941): 398–400. PMID 6646217 doi:10.1038/306398a0. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.
- ^ a b Kozak, M. (March 1983). "Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles." (PDF). Microbiological Reviews 47 (1): 1-45. PMID 6343825.
External links
- Life of mRNA Flash animation
- What, Who, Where and When about mRNA - GoPubMed
Dictionary
messenger RNA
-noun
- (biochemistry) RNA that encodes and carries information from DNA during transcription to sites of protein synthesis to undergo translation in order to yield a gene product.
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