Internal ribosome entry site
Encyclopedia
An internal ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

 entry site
, abbreviated IRES, is a nucleotide sequence that allows for translation
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...

 initiation in the middle of a messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

 (mRNA) sequence as part of the greater process of protein synthesis. Usually, in eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

s, translation can be initiated only at the 5' end of the mRNA molecule, since 5' cap
5' cap
The 5' cap is a specially altered nucleotide on the 5' end of precursor messenger RNA and some other primary RNA transcripts as found in eukaryotes. The process of 5' capping is vital to creating mature messenger RNA, which is then able to undergo translation...

 recognition is required for the assembly of the initiation complex.

History

These sequences were first discovered in 1988 in poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...

 RNA and encephalomyocarditis virus RNA in the labs of Nahum Sonenberg and Eckard Wimmer
Eckard Wimmer
Eckard Wimmer is an American virologist most famous for his seminal work on the molecular biology of poliovirus and the first chemical synthesis of a live virus.-Life and career:Wimmer was born on 22 May 1936 in Berlin, Germany...

, respectively. They are described as distinct regions of RNA molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

s that are able to attract the eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

 to the mRNA molecule and, therefore, allow translation initiation to occur. This process became known as the internal initiation of translation. It has been hypothesized that IRES elements have a distinct secondary
Secondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...

 or even tertiary structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...

, but similar structural features at the levels of either primary
Primary structure
The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...

 or secondary structure that are common to all IRES segments have not been reported to date.

Location

It is common that IRESes are located in the 5'UTR of RNA virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...

es and allow translation of the RNAs in a cap-independent manner. However, mRNAs of viruses from Dicistroviridae family possess two ORFs (open reading frames), translation of the both being directed by two distinct IRESes. It was later suggested that some mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

ian mRNAs also have IRES. Several cellular IRES elements are thought to be located in eukaryotic mRNAs encoding genes involved in stress survival, and other processes critical to survival. As of September 2009, there are 60 animal and 8 plant viruses reported to contain IRES segments and 115 mRNA sequences containing them as well.

Activation

IRES are often used by viruses as a means to ensure that viral translation is active during periods of time when host translation is inhibited. These mechanisms of host translation inhibition are varied, and can be initiated by both virus and host, depending on the type of virus in question. However, in the case of most picornaviruses, this is accomplished by the viral protease cleaving eIF-4G so that it cannot interact with eIF-4E. Interaction between these two initiation factor
Initiation factor
Initiation factors are proteins that bind to the small subunit of the ribosome during the initiation of translation, a part of protein biosynthesis.They are divided into three major groups:*Prokaryotic initiation factors*Archaeal initiation factors...

s is necessary for mRNA 5'cap to 3'poly-A-tail loop formation, which is usually a necessary event for initiation of translation. The virus may even use the eIF-4G to aid in initiation of IRES-mediated translation.

The cell may also use IRES to increase translation of certain proteins during mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

 and programmed cell death
Programmed cell death
Programmed cell-death is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process which generally confers advantage during an organism's life-cycle...

. In mitosis, the cell dephosphorylates eIF-4E so that it has little affinity for the 5'cap. As a result, the pre-initiation mRNA loop is not formed, and the translational machinery is diverted to IRES within the mRNA. Many proteins involved in mitosis are encoded by IRES mRNA. In programmed cell death, cleavage of eIF-4G, such as performed by viruses, decreases translation. Lack of essential proteins contributes to the death of the cell, as does translation of IRES mRNA sequences coding proteins involved in controlling cell death.

Mechanism

The mechanism of viral IRES function to date is better characterized than the mechanism of cellular IRES function, for which no clear mechanism have been proposed yet. Hepatitis C Virus
Hepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...

-related IRESs directly bind 40S
40S
40S is the small subunit of eukaryotic ribosomes.It interacts with the internal ribosome entry site of the hepatitis C virus.The following is a list of proteins contained in the 40S ribosome:...

 ribosomal subunit in such a way that their initiator codons are located in ribosomal P-site
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...

 without mRNA scanning. These IRESs do not require Eukaryotic initiation factors eIF1, 1A, 4A, 4B, and 4E. Picornavirus
Picornavirus
A picornavirus is a virus belonging to the family Picornaviridae. Picornaviruses are non-enveloped, positive-stranded RNA viruses with an icosahedral capsid. The genome RNA is unusual because it has a protein on the 5' end that is used as a primer for transcription by RNA polymerase...

 IRES do not attract 40S directly, but rather through high-affinity eIF4G
Eukaryotic translation
Eukaryotic translation is the process by which messenger RNA is translated into proteins in eukaryotes. It consists of initiation, elongation and termination Translation-Initiation:-Cap-dependent initiation:...

-binding site. In addition, many viral IRES (as well as cellular IRES) require additional proteins to mediate their function, known as IRES trans-acting factors (ITAFs). The role of ITAFs in IRES function is currently the subject of intense research.

Testing

Testing a particular RNA sequence for IRES activity relies on a bicistronic reporter construct. When an IRES segment is located between two reporter open reading frames in a eukaryotic mRNA molecule (a bicistronic mRNA), it can drive translation of the downstream protein coding region independently of the 5'-cap structure bound to the 5' end of the mRNA molecule. In such a setup both proteins are produced in the cell. The first reporter protein located in the first cistron is synthesized by the cap-dependent initiation approach while translation initiation of the second protein is directed by the IRES segment located in the intercistronic spacer region between the two reporter protein coding regions. However, there are several caveats to be aware of when interpreting data produced using bicistronic reporter constructs. For example, there are several known cases of mis-reported IRES segments that were later recognized as promoter-containing regions. More recently, splice acceptor sites within several presumed IRES segments have been shown to be responsible for apparent IRES function in bicistronic reporter assays.

Types

Internal ribosome entry sites in viral genomes
Virus IRES
Poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...

 
Picornavirus IRES
Picornavirus internal ribosome entry site (IRES)
This family represents the Picornavirus internal ribosome entry site . IRES elements allow cap and end-independent translation of mRNA in the host cell. It has been found that La autoantigen is required for Coxsackievirus B3 IRES-mediated translation, and it has been suggested that La may be...

Rhinovirus
Rhinovirus
Human rhinoviruses are the most common viral infective agents in humans and are the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures between 33–35 °C , and this may be why it occurs primarily in the nose...

 
Picornavirus IRES
Picornavirus internal ribosome entry site (IRES)
This family represents the Picornavirus internal ribosome entry site . IRES elements allow cap and end-independent translation of mRNA in the host cell. It has been found that La autoantigen is required for Coxsackievirus B3 IRES-mediated translation, and it has been suggested that La may be...

Encephalomyocarditis virus
Encephalomyocarditis virus
Encephalomyocarditis virus is a member of the Picornaviridae family. Infection with the virus causes encephalomyocarditis and reproductive disease in pigs. Although a variety of mammals may host the virus, pigs are classed as the domestic host as they are most easily infected...

 
Picornavirus IRES
Picornavirus internal ribosome entry site (IRES)
This family represents the Picornavirus internal ribosome entry site . IRES elements allow cap and end-independent translation of mRNA in the host cell. It has been found that La autoantigen is required for Coxsackievirus B3 IRES-mediated translation, and it has been suggested that La may be...

Foot-and-mouth disease virus
Foot-and-mouth disease virus
The foot-and-mouth disease virus is the pathogen that causes foot-and-mouth disease. It is a picornavirus, the prototypical member of the Aphthovirus genus...

 
Aphthovirus IRES
Aphthovirus internal ribosome entry site (IRES)
This family represents the internal ribosome entry site of the aphthoviruses. IRES elements allow cap and end-independent translation of mRNA in the host cell...

Hepatitis A virus  Hepatitis A IRES
Hepatitis A virus internal ribosome entry site (IRES)
This family represents the internal ribosome entry site of the Hepatitis A virus. IRES elements allow cap and end-independent translation of mRNA in the host cell...

Hepatitis C virus
Hepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...

 
Hepatitis C IRES
Hepatitis C virus internal ribosome entry site
Protein translation of most eukaryotic mRNAs requires association of Met-tRNA, several eukaryotic initiation factors, and GTP with the 40S ribosomal subunit. The ribosome can only bind the capped mRNA after binding to the initiator tRNA. Translation of hepatitis C virus mRNA is initiated by a...

Classical swine fever virus Pestivirus IRES
Pestivirus internal ribosome entry site (IRES)
This family represents the internal ribosome entry site of the pestiviruses. The pestivirus IRES allows cap and end-independent translation of mRNA in the host cell...

Bovine viral diarrhea virus  Pestivirus IRES
Pestivirus internal ribosome entry site (IRES)
This family represents the internal ribosome entry site of the pestiviruses. The pestivirus IRES allows cap and end-independent translation of mRNA in the host cell...

Friend
Friend virus
The Friend virus is a strain of murine leukemia virus identified by Charlotte Friend in 1956. The virus infects adult immunocompetent mice and is a well-established model for studying genetic resistance to infection by an immunosuppressive retrovirus. The Friend virus has been used for both...

 murine leukemia
Murine leukemia virus
The murine leukemia viruses are retroviruses named for their ability to cause cancer in murine hosts. Some MLVs may infect other vertebrates. MLVs include both exogenous and endogenous viruses...

 
Moloney murine leukemia
Murine leukemia virus
The murine leukemia viruses are retroviruses named for their ability to cause cancer in murine hosts. Some MLVs may infect other vertebrates. MLVs include both exogenous and endogenous viruses...

 (MMLV)
Rous sarcoma virus
Rous sarcoma virus
Rous sarcoma virus is a retrovirus and is the first oncovirus to have been described: it causes sarcoma in chickens.As with all retroviruses, it reverse transcribes its RNA genome into cDNA before integration into the host DNA.-History:...

 
Human immunodeficiency virus 
Plautia stali intestine virus  Cripavirus internal ribosome entry site (IRES)
Cripavirus internal ribosome entry site (IRES)
The Cripavirus internal ribosome entry site is an RNA element required for the production of capsid proteins through IRES-mediated translation....

Rhopalosiphum padi virus  Cripavirus internal ribosome entry site (IRES)
Cripavirus internal ribosome entry site (IRES)
The Cripavirus internal ribosome entry site is an RNA element required for the production of capsid proteins through IRES-mediated translation....

Cricket paralysis virus
Cricket paralysis virus
Cricket Paralysis Virus was initially discovered in Australian field crickets by Carl Reinganum and his colleagues at the Victorian Plant Research Institute . The paralytic disease spread rapidly through a breeding colony as well as through a laboratory population causing about 95% mortality...

 
Cripavirus internal ribosome entry site (IRES)
Cripavirus internal ribosome entry site (IRES)
The Cripavirus internal ribosome entry site is an RNA element required for the production of capsid proteins through IRES-mediated translation....

Triatoma virus  Cripavirus internal ribosome entry site (IRES)
Cripavirus internal ribosome entry site (IRES)
The Cripavirus internal ribosome entry site is an RNA element required for the production of capsid proteins through IRES-mediated translation....

Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...

 
Kaposi's sarcoma-associated herpesvirus IRES
Kaposi's sarcoma-associated herpesvirus internal ribosome entry site (IRES)
This family represents the Kaposi's sarcoma-associated herpesvirus internal ribosome entry site present in the vCyclin gene. The vCyclin and vFLIP coding sequences are present on a bicistronic transcript and it is thought the IRES may initiate translation of vFLIP from this bicistronic transcript....

Marek's disease virus MDV  5'Leader IRES and intercistronic IRES in the 1.8-kb family of immediate early transcripts (IRES)1

Internal ribosome entry sites in cellular mRNAs
Protein type Proteins
Growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....

s
Fibroblast growth factor
Fibroblast growth factor
Fibroblast growth factors, or FGFs, are a family of growth factors involved in angiogenesis, wound healing, and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal...

 (FGF-1 IRES
FGF-1 internal ribosome entry site (IRES)
The FGF-1 internal ribosome entry site is an RNA element present in the 5' UTR of the mRNA of fibroblast growth factor-1 and allows cap-independent translation. It is thought that FGF-1 internal ribosome entry site activity is strictly controlled and highly tissue specific....

 and FGF-2 IRES
FGF-2 internal ribosome entry site (IRES)
The FGF-2 internal ribosome entry site is an RNA element present in the 5' UTR of the mRNA of fibroblast growth factor-2. It has been found that the FGF-2 internal ribosome entry site activity is strictly controlled and highly tissue specific. It is thought that translational IRES dependent...

), Platelet-derived growth factor
Platelet-derived growth factor
In molecular biology, platelet-derived growth factor is one of the numerous growth factors, or proteins that regulate cell growth and division. In particular, it plays a significant role in blood vessel formation , the growth of blood vessels from already-existing blood vessel tissue. Uncontrolled...

 B (PDGF/c-sis IRES
C-sis internal ribosome entry site (IRES)
The c-sis internal ribosome entry site is a RNA element found in the 5' UTR of the PDGF beta chain gene. The internal ribosome entry site contains three modules that can individually mediate internal ribosome entry. However, the full length sequence is required for maximal IRES activity...

), Vascular endothelial growth factor
Vascular endothelial growth factor
Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....

 (VEGF IRES
Vascular endothelial growth factor (VEGF) IRES A
This family represents the vascular endothelial growth factor internal ribosome entry site A. VEGF is an endothelial cell mitogen with many crucial functions such as embryogenic development and wound healing. The 5' UTR of VEGF mRNA contains two IRES elements which are able to promote efficient...

), Insulin-like growth factor 2
Insulin-like growth factor 2
Insulin-like growth factor 2 is one of three protein hormones that share structural similarity to insulin.-Gene structure:In humans, the IGF2 gene is located on chromosome 11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at distal chromosome 7...

 (IGF-II IRES
Insulin-like growth factor II IRES
The insulin-like growth factor II internal ribosome entry site IRES is found in the 5' UTR of IGF-II leader 2 mRNA. This RNA element allows cap-independent translation of the mRNA and it is thought that this family may facilitate a continuous IGF-II production in rapidly dividing cells during...

)
Transcription factors  Antennapedia
Antennapedia
Antennapedia is a HOM-C gene first discovered in Drosophila which controls the formation of legs during development. Loss-of-function mutations in the regulatory region of this gene result in the development of the second leg pair into ectopic antennae...

, Ultrabithorax
Ultrabithorax
Ultrabithorax or Ubx is a member of the homeobox gene family. Homeobox proteins function as transcription factors. In Drosophila melanogaster it is expressed in the third thoracic and first abdominal segments and represses wing formation. The Ubx gene regulates the decisions regarding the...

, MYT-2, NF-κB repressing factor NRF, AML1/RUNX1
RUNX1
Runt-related transcription factor 1 also known as acute myeloid leukemia 1 protein or core-binding factor subunit alpha-2 is a protein that in humans is encoded by the RUNX1 gene....

, Gtx homeodomain protein
Translation factor
Translation
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. Whereas interpreting undoubtedly antedates writing, translation began only after the appearance of written literature; there exist partial translations of the Sumerian Epic of...

s
Eukaryotic initiation factor
Eukaryotic initiation factor
Eukaryotic initiation factors are proteins involved in the initiation phase of eukaryotic translation. They function in forming a complex with the 40S ribosomal subunit and Met-tRNAi called the 43S preinitation complex , recognizing the 5' cap structure of mRNA and recruiting the 43S PIC to mRNA,...

 4G (elF4G)a, Eukaryotic initiation factor 4Gl (elF4Gl)a, Death associated protein 5 (DAP5)
Oncogene
Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...

s
c-myc
C-myc internal ribosome entry site (IRES)
The c-myc internal ribosome entry site is an RNA element present in the 5' UTR of the mRNA of C-myc and allows cap-independent translation. The mammalian c-myc gene is a proto-oncogene which is required for cell proliferation, transformation and death...

, L-myc
L-myc internal ribosome entry site (IRES)
The L-myc internal ribosome entry site is an RNA element present in the 5' UTR of the mRNA of L-myc that allows cap-independent translation. L-myc undergoes translation via the internal ribosome entry site and bypasses the typical eukaryotic cap-dependent translation pathway [1]...

, Pim-1, Protein kinase p58PITSLRE, p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

Transporter
Transporter
Transporter may refer to:* Transporter , types of vehicles designed to transport items* Volkswagen Transporter, a model of van- Film and television :...

s/receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

s
Cationic amino acid transporter Cat-1, Nuclear form of Notch
Notch
Notch may refer to:* The nock of an arrow* Notch , a Hip hop, R&B, reggae, dancehall and reggaeton artist* Notch signaling pathway, a cell signaling system present in most multicellular organisms...

 2, Voltage-gated potassium channel
Voltage-gated potassium-channel Kv1.4 IRES
This family represents the Kv1.4 voltage-gated potassium channel internal ribosome entry site . This region has been shown to mediate internal ribosome entry in cells derived from brain, heart, and skeletal muscle; tissues known to express Kv1.4 mRNA species....

Activators of apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 
Apoptotic protease activating factor (Apaf-1)
Inhibitors of apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 
X-linked inhibitor of apoptosis (XIAP
XIAP
X-linked inhibitor of apoptosis protein also known as inhibitor of apoptosis protein 3 and baculoviral IAP repeat-containing protein 4 is a protein that in humans is encoded by the XIAP gene....

), HIAP2, Bcl-xL
Bcl-xL
B-cell lymphoma-extra large is a transmembrane molecule in the mitochondria. It is involved in the signal transduction pathway of the FAS-L. It is one of several anti-apoptotic proteins which are members of the Bcl-2 family of proteins. It has been implicated in the survival of cancer cells. Other...

, Bcl-2
Bag-1 internal ribosome entry site (IRES)
The bag-1 internal ribosome entry site is a cis-acting element located in the 5 ' untranslated region of the BAG-1 protein mRNA. Its effects apoptosis through IRES mediated translation of the BAG-1 protein....

Proteins localized in neuronal dendrites  Activity-regulated cytoskeletal protein (ARC
ARC
ARC may refer to:- Business :* African Rainforest Conservancy, an environmental nonprofit* Airport Regions Conference, a European organization of major airports* Amalgamated Roadstone Corporation, a British stone quarrying company...

), α-subunit of calcium calmodulin dependent kinase
Ca2+/calmodulin-dependent protein kinase
/calmodulin-dependent protein kinases II or CaM kinases II are serine/threonine-specific protein kinases that are regulated by the /calmodulin complex...

 II dendrin, Microtubule-associated protein
Microtubule-associated protein
In cell biology, microtubule-associated proteins are proteins that interact with the microtubules of the cellular cytoskeleton.-Function:...

 2 (MAP2), neurogranin
Neurogranin
Neurogranin is a calmodulin-binding protein expressed exclusively in the brain, particularly in dendritic spines, and participating in the protein kinase C signaling pathway. Neurogranin is the main postsynaptic protein regulating the availability of calmodulin, binding to it in the absence of...

 (RC3), Amyloid precursor protein
Amyloid precursor protein
Amyloid precursor protein is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation, neural plasticity and iron export...

Others Immunoglobulin heavy chain
Heavy chain
]The immunoglobulin heavy chain is the large polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains. Several different types of heavy chain exist that define the class or isotype of an antibody. These heavy chain types vary...

 binding protein (BiP)
Bip internal ribosome entry site (IRES)
The BiP internal ribosome entry site is an RNA element present in the 5' UTR of the mRNA of BiP protein and allows cap-independent translation. BiP protein expression has been found to be significantly enhanced by the heat shock response due to internal ribosome entry site -dependent translation...

, Heat shock protein 70
Heat shock protein 70 (Hsp70) internal ribosome entry site (IRES)
The heat shock protein 70 internal ribosome entry site is an RNA element that allows cap independent translation during conditions such as heat shock and stress. It has been shown that the 216 nucleotide long 5' UTR contains internal ribosome entry site activity....

, β-subunit of mitochondrial H+-ATP synthase, Ornithine decarboxylase
Ornithine decarboxylase
The enzyme ornithine decarboxylase catalyzes the decarboxylation of ornithine to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids and forms a homodimer....

, connexins  32
Connexin-32 internal ribosome entry site (IRES)
The connexin-32 internal ribosome entry site is an RNA element present in the 5' UTR of the mRNA of connexin-32 and allows cap-independent translation. This internal ribosome entry site allows cap independent translation during conditions such as heat shock and stress....

 and 43
Connexin-43 internal ribosome entry site (IRES)
The connexin-43 internal ribosome entry site is an RNA element present in the 5' UTR of the mRNA of connexin-43 and allows cap-independent translation. The connexin-43 internal ribosome entry site allows cap independent translation during conditions such as heat shock and stress....

, HIF-1α
HIF-1 alpha IRES
The HIF-1α internal ribosome entry site is an RNA element present in the 5' UTR of the mRNA of HIF-1α that allows cap-independent translation. The HIF-1α internal ribosome entry site allows translation to be maintained under hypoxic cell conditions that inhibit cap-dependent translation [1]...

, APC
APC internal ribosome entry site (IRES)
The APC internal ribosome entry site is an RNA element which is located in the coding sequence of the APC gene. APC is a tumour suppressor gene which is associated with the inherited disease adenomatous polyposis coli . It is thought that IRES-mediated translation of APC is important for an...




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