Translational frameshift
Encyclopedia
Translational frameshifting or ribosomal frameshifting refers to an alternate process of protein
translation
. A protein is translated from one end of the mRNA to the other, from the 5' to the 3' end. Normally a protein is translated from a template mRNA with consecutive blocks of 3 nucleotides being read as single amino acids. However, certain organisms may exhibit a change or shift in the ribosomes frame
by one or two nucleotides when translating the genetic code
. This is deemed translational or ribosomal frameshifting. The process can be programmed by the nucleotide
sequence of the mRNA and is sometimes affected by the secondary or tertiary mRNA structure. It has been described mainly in viruses (especially retroviruses), retrotransposons and bacterial insertion elements, and also in some cellular genes.
. For example, the following sentence when read from the beginning makes sense to a reader:
|Start|THE CAT AND THE MAN ARE FAT ...
|Start|123 123 123 123 123 123 123 ...
However, changing the reading frame by say shifting the first reading up one letter between the T and H on the first word:
T|Start|HEC ATA NDT HEM ANA REF AT...
-|Start|123 123 123 123 123 123 12...
Now the sentence makes absolutely no sense. In the case of a translating ribosome
, a frameshift can result in nonsense being created after the frameshift or a completely different protein being created after the frameshift. When referring to translational frameshifting, the latter is always inferred, the former being a usual unfortunate result of a point mutation
such as a deletion.
frameshifting is that there are a few mechanisms used to control the latter. All are based on the fact that ribosomes do not translate proteins at a steady rate regardless of the sequence. There are certain codons that take longer to translate because there are not equal amounts of tRNA of that particular codon in the cytosol
. Hence there exists sequences known as choke points (small sections of harder to find codons, resulting in a slowed ribosome translation) and slippery sequences (small sections of very easily accessible codons, resulting in a quick ribosome translation) that control the rate of ribosomal frameshifting. Slippery sequences can potentially make the reading ribosome "slip" and skip a number of nucleotides (usually only 1) and read a completely different frame thereafter. Choke points reduce the probability of this happening.
) and some cellular genes (e.g. prfB a release factor
). Its use is primarily for compacting more gene
tic information into a shorter amount of genetic material.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
translation
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...
. A protein is translated from one end of the mRNA to the other, from the 5' to the 3' end. Normally a protein is translated from a template mRNA with consecutive blocks of 3 nucleotides being read as single amino acids. However, certain organisms may exhibit a change or shift in the ribosomes frame
Reading frame
In biology, a reading frame is a way of breaking a sequence of nucleotides in DNA or RNA into three letter codons which can be translated in amino acids. There are 3 possible reading frames in an mRNA strand: each reading frame corresponding to starting at a different alignment...
by one or two nucleotides when translating the genetic code
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
. This is deemed translational or ribosomal frameshifting. The process can be programmed by the nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
sequence of the mRNA and is sometimes affected by the secondary or tertiary mRNA structure. It has been described mainly in viruses (especially retroviruses), retrotransposons and bacterial insertion elements, and also in some cellular genes.
Process overview
Proteins are translated unidirectionally by reading tri-nucleotides on the mRNA strand also known as codons. Therefore, a shift of any number of nucleotides that is not divisible by 3 in the reading frame will result in subsequent codons to be read differently. This effectively changes the ribosomal reading frameReading frame
In biology, a reading frame is a way of breaking a sequence of nucleotides in DNA or RNA into three letter codons which can be translated in amino acids. There are 3 possible reading frames in an mRNA strand: each reading frame corresponding to starting at a different alignment...
. For example, the following sentence when read from the beginning makes sense to a reader:
|Start|THE CAT AND THE MAN ARE FAT ...
|Start|123 123 123 123 123 123 123 ...
However, changing the reading frame by say shifting the first reading up one letter between the T and H on the first word:
T|Start|HEC ATA NDT HEM ANA REF AT...
-|Start|123 123 123 123 123 123 12...
Now the sentence makes absolutely no sense. In the case of a translating 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....
, a frameshift can result in nonsense being created after the frameshift or a completely different protein being created after the frameshift. When referring to translational frameshifting, the latter is always inferred, the former being a usual unfortunate result of a point mutation
Point mutation
A point mutation, or single base substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA. Often the term point mutation also includes insertions or deletions of a single base pair...
such as a deletion.
Controlling mechanisms
The main differences between a frameshift as a result of mutation and a frameshift as a result of ribosomalRibosome
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....
frameshifting is that there are a few mechanisms used to control the latter. All are based on the fact that ribosomes do not translate proteins at a steady rate regardless of the sequence. There are certain codons that take longer to translate because there are not equal amounts of tRNA of that particular codon in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
. Hence there exists sequences known as choke points (small sections of harder to find codons, resulting in a slowed ribosome translation) and slippery sequences (small sections of very easily accessible codons, resulting in a quick ribosome translation) that control the rate of ribosomal frameshifting. Slippery sequences can potentially make the reading ribosome "slip" and skip a number of nucleotides (usually only 1) and read a completely different frame thereafter. Choke points reduce the probability of this happening.
Examples
This type of frameshifting may be programmed to occur at particular recoding sites and is important in some viruses (e.g. SARS, HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
) and some cellular genes (e.g. prfB a release factor
Release factor
A release factor is a protein that allows for the termination of translation by recognizing the termination codon or stop codon in a mRNA sequence....
). Its use is primarily for compacting more gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
tic information into a shorter amount of genetic material.
| Type | Distribution | Ref. |
|---|---|---|
| ALIL pseudoknot ALIL pseudoknot ALIL pseudoknot is an RNA element that induces frameshifting in bacteria. The expression of a minority of genes requires frameshifting to occur where the frequency of frameshifting is increased by a RNA secondary structure located on the 3' side of the shift site... |
Bacteria Bacteria Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals... |
|
| Antizyme RNA frameshifting stimulation element Antizyme RNA frameshifting stimulation element Antizyme RNA frameshifting stimulation element is a structural element which is found in antizyme mRNA and is known to promote frameshifting. Antizyme genes have two partially overlapping open reading frames, the second, which encodes the functional protein requires +1 translational frameshifting... |
Invertebrate Invertebrate An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group... s |
|
| Coronavirus frameshifting stimulation element Coronavirus frameshifting stimulation element In molecular biology, the coronavirus frameshifting stimulation element is a conserved stem-loop of RNA found in coronaviruses that can promote ribosomal frameshifting. Such RNA molecules interact with a downstream region to form a pseudoknot structure; the region varies according to the virus but... |
Coronavirus Coronavirus Coronaviruses are species in the genera of virus belonging to the subfamily Coronavirinae in the family Coronaviridae. Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome and a helical symmetry. The genomic size of coronaviruses ranges from approximately 16 to 31... |
|
| DnaX ribosomal frameshifting element DnaX ribosomal frameshifting element The DnaX ribosomal frameshifting element is a RNA element found in the mRNA of the dnaX gene in E. coli. The dnaX gene has two encoded products tau and gamma which are produced in a 1:1 ratio. The gamma protein is synthesised due to programmed frameshifting and is shorter than tau. The two products... |
Eukaryota, Bacteria Bacteria Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals... |
|
| HIV Ribosomal frameshift signal HIV Ribosomal frameshift signal The HIV ribosomal frameshift signal is an RNA element. HIV uses a system called −1 ribosomal frameshifting to produce the required ratio of Gag and Gag-Pol polyproteins. The stem-loop structure of the frameshift signal is thought to impede the ribosome and cause slippage in the 5' direction, this... |
Viruses | |
| Insertion sequence IS1222 ribosomal frameshifting element Insertion sequence IS1222 ribosomal frameshifting element The Insertion sequence IS1222 ribosomal frameshifting element is an RNA element found in the insertion sequence IS222. The ribosomal frameshifting element stimulates frameshifting which is known to be required for transposition.... |
Eukaryota, Bacteria Bacteria Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals... |
|
| Ribosomal frameshift Ribosomal frameshift A ribosomal frameshift allows alternative translation of a mRNA sequence by changing the open reading frame. It is commonly found in viruses including barley yellow dwarf virus, potato leafroll virus and simian retrovirus-1. Ribosomal frameshifting is promoted by a pseudoknot structure and slippery... |
Viruses | |
See also
- Antizyme RNA frameshifting stimulation elementAntizyme RNA frameshifting stimulation elementAntizyme RNA frameshifting stimulation element is a structural element which is found in antizyme mRNA and is known to promote frameshifting. Antizyme genes have two partially overlapping open reading frames, the second, which encodes the functional protein requires +1 translational frameshifting...
- Coronavirus frameshifting stimulation elementCoronavirus frameshifting stimulation elementIn molecular biology, the coronavirus frameshifting stimulation element is a conserved stem-loop of RNA found in coronaviruses that can promote ribosomal frameshifting. Such RNA molecules interact with a downstream region to form a pseudoknot structure; the region varies according to the virus but...
- DnaX ribosomal frameshifting elementDnaX ribosomal frameshifting elementThe DnaX ribosomal frameshifting element is a RNA element found in the mRNA of the dnaX gene in E. coli. The dnaX gene has two encoded products tau and gamma which are produced in a 1:1 ratio. The gamma protein is synthesised due to programmed frameshifting and is shorter than tau. The two products...
- Frameshift mutationFrameshift mutationA frameshift mutation is a genetic mutation caused by indels of a number of nucleotides that is not evenly divisible by three from a DNA sequence...
- HIV Ribosomal frameshift signalHIV Ribosomal frameshift signalThe HIV ribosomal frameshift signal is an RNA element. HIV uses a system called −1 ribosomal frameshifting to produce the required ratio of Gag and Gag-Pol polyproteins. The stem-loop structure of the frameshift signal is thought to impede the ribosome and cause slippage in the 5' direction, this...
- Insertion sequence IS1222 ribosomal frameshifting elementInsertion sequence IS1222 ribosomal frameshifting elementThe Insertion sequence IS1222 ribosomal frameshifting element is an RNA element found in the insertion sequence IS222. The ribosomal frameshifting element stimulates frameshifting which is known to be required for transposition....
- Recode databaseRecode (database)RECODE is a database of 'programmed' frameshifts, bypassing and codon redefinition used for gene expression....
- Ribosomal frameshiftRibosomal frameshiftA ribosomal frameshift allows alternative translation of a mRNA sequence by changing the open reading frame. It is commonly found in viruses including barley yellow dwarf virus, potato leafroll virus and simian retrovirus-1. Ribosomal frameshifting is promoted by a pseudoknot structure and slippery...
External links
- Wise2 - aligns a proteinProteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
against a DNADNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
sequence allowing frameshifts and intronIntronAn intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
s - FastY - compare a DNADNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
sequence to a proteinProteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
sequence database, allowing gaps and frameshifts - Path - tool that compares two frameshift proteins (back-translationTranslation (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...
principle) - Recode2 - Database of recoded genes, including those that require programmed Translational frameshift.