Messenger RNA 20232 222486335 2008-06-29T16:30:35Z DOI bot 6652755 Citation maintenance. Formatted: title. Initiated by [[User:Fconaway|Fconaway]]. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. [[Image:MRNA-interaction.png|thumb|300px| The "life cycle" of an '''mRNA''' in a eukaryotic cell. RNA is [[transcription (genetics)|transcribed]] in the [[cell nucleus|nucleus]]; once completely processed, it is transported to the [[cytoplasm]] and [[Translation (genetics)|translated]] by the [[ribosome]]. At the end of its life, the mRNA is degraded.]] '''Messenger ribonucleic acid''' ('''mRNA''') is a molecule of [[RNA]] encoding a chemical "blueprint" for a [[protein]] product. mRNA is [[transcription (genetics)|transcribed]] from a [[DNA]] template, and carries coding information to the sites of [[protein synthesis]]: the [[ribosomes]]. Here, the nucleic acid polymer is [[translation (genetics)|translated]] into a polymer of [[amino acids]]: a protein. In mRNA as in DNA, genetic information is encoded in the sequence of four [[nucleotides]] arranged into [[codons]] of three bases each. Each codon encodes for a specific [[amino acid]], except the [[stop codon]]s that terminate protein synthesis. 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. ==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. [[eukaryotes|Eukaryotic]] mRNA molecules often require extensive processing and transport, while [[prokaryote|prokaryotic]] molecules do not. ===Transcription=== {{main|Transcription (genetics)}} During transcription, [[RNA polymerase]] makes a copy of a gene from the DNA to mRNA as needed. 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]]''. === Eukaryotic pre-mRNA processing === {{main|Post-transcriptional modification}} Processing of mRNA differs greatly among [[eukaryote]]s, [[bacteria]] and [[archea]]. 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 ==== {{main|5' cap}} A ''5' cap'' (also termed an RNA cap, an RNA 7-methylguanosine cap or an RNA m<sup>7</sup>G 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 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 [[RNase]]s. 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]]. This [[enzyme|enzymatic]] complex [[catalyze]]s the chemical reactions that are required for mRNA capping. Synthesis proceeds as a multi-step [[biochemistry|biochemical]] reaction. ==== Splicing ==== {{main|Splicing (genetics)}} Splicing is the process by which pre-mRNA is modified to remove certain stretches of non-coding sequences called [[intron]]s; the stretches that remain include protein-coding sequences and are called [[exon]]s. 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]]. 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 [[ribozyme]]s''). ====Editing==== In some instances, an mRNA will be [[RNA editing|edited]], changing the nucleotide composition of that mRNA. 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 ==== {{main|Polyadenylation}} Polyadenylation is the covalent linkage of a polyadenylyl moiety to a messenger RNA molecule. In eukaryotic organisms, most messenger RNA (mRNA) molecules are polyadenylated at the 3' end. The [[messenger RNA#3' poly(A) tail|poly(A) tail]] and the protein bound to it aid in protecting mRNA from degradation by exonucleases. 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. Just as in alternative splicing, there can be more than one polyadenylation variant of a mRNA. ===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 [[cell nucleus|nucleus]] to the [[cytoplasm]]. Mature mRNAs are recognized by their processed modifications and then exported through the [[nuclear pore]]. ===Translation=== {{main|Translation (genetics)}} Because prokaryotic mRNA does not need to be processed or transported, '''translation''' by the [[ribosome]] can begin immediately after the end of transcription. 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]]. Therefore, unlike prokaryotes, eukaryotic translation ''is not'' directly coupled to transcription. ===Degradation=== After a certain amount of time, the message is degraded by [[RNase]]s. 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 element]]s in some mammalian mRNAs tends to destabilize those transcripts through the action of cellular proteins that bind these motifs. Rapid mRNA degradation via [[AU-rich element]]s 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).<ref name="Shaw1986">{{cite journal |author=Shaw G, Kamen R |title=A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation |journal=Cell |volume=46 |issue=5 |pages=659–67 |year=1986 |month=August |pmid=3488815 |doi=10.1016/0092-8674(86)90341-7}}</ref> Base pairing with a small interfering RNA ([[siRNA]]) or microRNA ([[miRNA]]) can also accelerate mRNA degradation. == mRNA structure == [[Image:MRNA structure.png|thumb|700px|center|The structure of a mature eukaryotic mRNA. A fully processed mRNA includes a [[5' cap]], [[5' UTR]], [[coding region]], [[3' UTR]], and poly(A) tail.]] === 5' cap === {{main|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. 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 === {{main|Coding region}} Coding regions are composed of [[codons]], which are decoded and translated into one (mostly eukaryotes) or several (mostly prokaryotes) proteins by the ribosome. Coding regions begin with the [[start codon]] and end with the one of three possible [[stop codon| stop codons]]. In addition to protein-coding, portions of coding regions may also serve as regulatory sequences in the [[pre-mRNA]] as [[exonic splicing enhancer]]s or [[exonic splicing silencer]]s. Start codons are indicated by a AUG triplet. Stop codons are indicated by a UAA, UAG, or UGA. === Untranslated regions === {{main|5' UTR|3' UTR}} 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. These regions are transcribed with the coding region and thus are [[exon]]ic as they are present in the mature mRNA. Several roles in gene expression have been attributed to the untranslated regions, including mRNA stability, mRNA localization, and [[translational efficiency]]. 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 [[ribonuclease]]s and for ancillary proteins that can promote or inhibit RNA degradation. 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. [[microRNA| MicroRNA]]s bound to the [[3' UTR]] also may affect translational efficiency or mRNA stability. 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. These structural mRNA elements are involved in regulating the mRNA. Some, such as the [[SECIS element]], are targets for proteins to bind. One class of mRNA element, the [[riboswitch]]es, directly bind small molecules, changing their fold to modify levels of transcription or translation. In these cases, the mRNA regulates itself. ===3' poly(A) tail===<!-- This section is linked from [[Messenger RNA]] --> {{main|Polyadenylation}} 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. 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.<ref>{{cite journal | author=Higgs DR, Goodbourn SE, Lamb J, Clegg JB, Weatherall DJ, Proudfoot NJ. | title=α-thalassaemia caused by a polyadenylation signal mutation | journal=Nature | year=1983 | volume=306 | issue=5941 | pages= 398–400 | url = http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v306/n5941/abs/306398a0.html | pmid = 6646217 {{doi|10.1038/306398a0}} | doi=10.1038/306398a0 }}</ref> === Monocistronic versus polycistronic mRNA === An mRNA molecule is said to be monocistronic when it contains the genetic information to [[Translation (genetics)|translate]] only a single [[protein]]. This is the case for most of the [[Eukaryote|eukaryotic]] mRNAs<ref name="Kozak_1983"> {{ cite journal | author = Kozak, M. | year = 1983 | month = March | title = Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles | journal = Microbiological Reviews | volume = 47 | issue = 1 | pages = 1–45 | doi = | pmid = 6343825 | url = http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=281560&blobtype=pdf | format = PDF | accessdate = 2006-08-12 }} </ref>. 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<ref name="Kozak_1983"/>. Dicistronic is the term used to describe a mRNA that encodes only two [[proteins]]. ==References== {{reflist}} ==External links== * [http://www.sumanasinc.com/webcontent/anisamples/molecularbiology/lifecyclemrna_fla.html Life of mRNA] Flash animation {{Nucleic acids}} [[Category:RNA]] [[Category:Gene expression]] [[Category:Protein biosynthesis]] [[Category:Genetics]] [[Category:Molecular genetics]] [[ar:مرسال الحمض النووي الريبي]] [[bg:Информационна РНК]] [[ca:ARN missatger]] [[cs:MRNA]] [[da:MRNA]] [[de:MRNA]] [[et:Informatsiooni-RNA]] [[es:ARN mensajero]] [[fr:Acide ribonucléique messager]] [[id:MRNA]] [[it:RNA messaggero]] [[he:MRNA]] [[la:MRNA]] [[lt:IRNR]] [[nl:Messenger RNA]] [[ja:伝令RNA]] [[oc:Acid ribonucleïc messatgèr]] [[pl:MRNA]] [[pt:ARN mensageiro]] [[ro:ARN mesager]] [[ru:МРНК]] [[sk:Mediátorová ribonukleová kyselina]] [[fi:Lähetti-RNA]] [[sv:Budbärar-RNA]] [[vi:RNA thông tin]] [[tr:MRNA]] [[uk:Матрична рибонуклеїнова кислота]] [[ur:پیامبر آر این اے]] [[zh:MRNA]]