Просмотр кода страницы Ribosomal frameshift

{{short description|Phenomenon that occurs during translation of a messenger RNA into proteins}}
'''[[Ribosome|Ribosomal]] frameshifting''', also known as '''translational frameshifting''' or '''translational recoding''', is a biological phenomenon that occurs during [[Translation (biology)|translation]] that results in the production of multiple, unique [[protein]]s from a single [[Messenger RNA|mRNA]].<ref>{{cite journal | vauthors = Atkins JF, Loughran G, Bhatt PR, Firth AE, Baranov PV | title = Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use | journal = Nucleic Acids Research | volume = 44 | issue = 15 | pages = 7007–7078 | date = September 2016 | pmid = 27436286 | pmc = 5009743 | doi = 10.1093/nar/gkw530 }}</ref> The process can be programmed by the [[nucleotide]] sequence of the mRNA and is sometimes affected by the [[Nucleic acid secondary structure|secondary, 3-dimensional mRNA structure]].<ref name=":02">{{cite journal | vauthors = Napthine S, Ling R, Finch LK, Jones JD, Bell S, Brierley I, Firth AE | title = Protein-directed ribosomal frameshifting temporally regulates gene expression | journal = Nature Communications | volume = 8 | article-number = 15582 | date = June 2017 | pmid = 28593994 | pmc = 5472766 | doi = 10.1038/ncomms15582 | bibcode = 2017NatCo...815582N }}</ref> It has been described mainly in [[viruses]] (especially [[retroviruses]]), [[retrotransposons]] and [[Bacteria|bacterial]] insertion elements, and also in some cellular [[Gene|genes]].<ref name=":1">{{cite journal | vauthors = Ketteler R | title = On programmed ribosomal frameshifting: the alternative proteomes | language = English | journal = Frontiers in Genetics | volume = 3 | page = 242 | date = 2012 | pmid = 23181069 | pmc = 3500957 | doi = 10.3389/fgene.2012.00242 | doi-access = free }}</ref>

Small molecules, proteins, and nucleic acids have also been found to stimulate levels of frameshifting. In December 2023, it was reported that ''in vitro''-transcribed (IVT) [[mRNA]]s in response to [[BNT162b2]] (Pfizer–BioNTech) anti-COVID-19 vaccine caused ribosomal frameshifting.<ref name="nature">{{Cite journal |last1=Mulroney |first1=Thomas E. |last2=Pöyry |first2=Tuija |last3=Yam-Puc |first3=Juan Carlos |last4=Rust |first4=Maria |last5=Harvey |first5=Robert F. |last6=Kalmar |first6=Lajos |last7=Horner |first7=Emily |last8=Booth |first8=Lucy |last9=Ferreira |first9=Alexander P. |last10=Stoneley |first10=Mark |last11=Sawarkar |first11=Ritwick |last12=Mentzer |first12=Alexander J. |last13=Lilley |first13=Kathryn S. |last14=Smales |first14=C. Mark |last15=von der Haar |first15=Tobias |date=2023-12-06 |title=N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting |journal=Nature |volume=625 |issue=7993 |language=en |pages=189–194 |doi=10.1038/s41586-023-06800-3 |issn=1476-4687|doi-access=free |pmid=38057663 |pmc=10764286 }}</ref>

== Process overview ==
Proteins are translated by reading tri-nucleotides on the mRNA strand, also known as [[codons]], from one end of the [[Messenger RNA|mRNA]] to the other (from the [[5' end|5']] to the [[3' end]]) starting with the amino acid [[methionine]] as the start (initiation) codon AUG.  Each codon is translated into a single [[amino acid]]. The code itself is considered [[Degeneracy (biology)|degenerate]], meaning that a particular amino acid can be specified by more than one codon. However, a shift of any number of nucleotides that is not divisible by 3 in the reading frame will cause subsequent codons to be read differently.<ref>{{cite journal | vauthors = Ivanov IP, Atkins JF | title = Ribosomal frameshifting in decoding antizyme mRNAs from yeast and protists to humans: close to 300 cases reveal remarkable diversity despite underlying conservation | journal = Nucleic Acids Research | volume = 35 | issue = 6 | pages = 1842–1858 | year = 2007 | pmid = 17332016 | pmc = 1874602 | doi = 10.1093/nar/gkm035 }}</ref> This effectively changes the ribosomal [[reading frame]].

=== Sentence example ===
In this example, the following sentence of three-letter words makes sense when read from the beginning:
 |Start|'''T'''HE CAT AND THE MAN ARE FAT ...
 |Start|123 123 123 123 123 123 123 ...

However, if the reading frame is shifted by one letter to between the '''T''' and H of the first word (effectively a +1 frameshift when considering the 0 position to be the initial position of '''T'''),
 '''T'''|Start|HEC ATA NDT HEM ANA REF AT...
 -|Start|123 123 123 123 123 123 12...

then the sentence reads differently, making no sense.

=== DNA example ===
In this example, the following sequence is a region of the [[human mitochondrial genome]] with the two [[overlapping genes]] [[MT-ATP8]] and [[MT-ATP6]].
When read from the beginning, these codons make sense to a ribosome and can be translated into amino acids (AA) under the [[vertebrate mitochondrial code]]:
 |Start|'''A'''AC GAA AAT CTG TTC GCT TCA ...
 |Start|123 123 123 123 123 123 123 ...
 | AA  | N   E   N   L   F   A   S  ...

However, let's change the reading frame by starting one nucleotide downstream (effectively a "+1 frameshift" when considering the 0 position to be the initial position of '''A'''):
 '''A'''|Start|ACG AAA ATC TGT TCG CTT CA...
 -|Start|123 123 123 123 123 123 12...
  | AA  | T   K   I   C   S   L    ...
Because of this +1 frameshifting, the DNA sequence is read differently. The different codon reading frame therefore yields different amino acids.

===Effect===
In the case of a translating ribosome, a frameshift can either result in [[nonsense mutation]], a premature [[stop codon]] after the frameshift, or the creation of a completely new protein after the frameshift. In the case where a frameshift results in nonsense, the [[Nonsense-mediated decay|nonsense-mediated mRNA decay]] (NMD) pathway may destroy the mRNA transcript, so frameshifting would serve as a method of [[Regulation of gene expression|regulating]] the [[Gene expression|expression]] level of the associated gene.<ref name=":3">{{cite journal | vauthors = Dever TE, Dinman JD, Green R | title = Translation Elongation and Recoding in Eukaryotes | journal = Cold Spring Harbor Perspectives in Biology | volume = 10 | issue = 8 | article-number = a032649 | date = August 2018 | pmid = 29610120 | pmc = 6071482 | doi = 10.1101/cshperspect.a032649 }}</ref>

If a novel or off-target protein is produced, it can trigger other unknown consequences.<ref name="nature"/>

== Function in viruses and eukaryotes ==
In viruses this phenomenon may be programmed to occur at particular sites and allows the virus to encode multiple types of proteins from the same mRNA. Notable examples include [[HIV-1]] (human immunodeficiency virus),<ref name=":4">{{cite journal | vauthors = Jacks T, Power MD, Masiarz FR, Luciw PA, Barr PJ, Varmus HE | title = Characterization of ribosomal frameshifting in HIV-1 gag-pol expression | journal = Nature | volume = 331 | issue = 6153 | pages = 280–283 | date = January 1988 | pmid = 2447506 | doi = 10.1038/331280a0 | bibcode = 1988Natur.331..280J | s2cid = 4242582 }}</ref> RSV ([[Rous sarcoma virus]])<ref name=":6">{{cite journal | vauthors = Jacks T, Madhani HD, Masiarz FR, Varmus HE | title = Signals for ribosomal frameshifting in the Rous sarcoma virus gag-pol region | journal = Cell | volume = 55 | issue = 3 | pages = 447–458 | date = November 1988 | pmid = 2846182 | doi = 10.1016/0092-8674(88)90031-1 | pmc = 7133365 }}</ref> and the [[influenza]] virus (flu),<ref>{{cite journal | vauthors = Jagger BW, Wise HM, Kash JC, Walters KA, Wills NM, Xiao YL, Dunfee RL, Schwartzman LM, Ozinsky A, Bell GL, Dalton RM, Lo A, Efstathiou S, Atkins JF, Firth AE, Taubenberger JK, Digard P | title = An overlapping protein-coding region in influenza A virus segment 3 modulates the host response | journal = Science | volume = 337 | issue = 6091 | pages = 199–204 | date = July 2012 | pmid = 22745253 | pmc = 3552242 | doi = 10.1126/science.1222213 | bibcode = 2012Sci...337..199J }}</ref> which all rely on frameshifting to create a proper ratio of 0-frame (normal translation) and "trans-frame" (encoded by frameshifted sequence) proteins. Its use in viruses is primarily for compacting more genetic information into a shorter amount of genetic material.

In eukaryotes it appears to play a role in regulating gene expression levels by generating premature stops and producing nonfunctional transcripts.<ref name=":1" /><ref name=":2">{{cite journal | vauthors = Advani VM, Dinman JD | title = Reprogramming the genetic code: The emerging role of ribosomal frameshifting in regulating cellular gene expression | journal = BioEssays | volume = 38 | issue = 1 | pages = 21–26 | date = January 2016 | pmid = 26661048 | pmc = 4749135 | doi = 10.1002/bies.201500131 }}</ref>

== Types of frameshifting ==
The most common type of frameshifting is '''−1 frameshifting''' or '''programmed −1 ribosomal frameshifting (−1 PRF)'''. Other, rarer types of frameshifting include +1 and −2 frameshifting.<ref name=":02" /> −1 and +1 frameshifting are believed to be controlled by different mechanisms, which are discussed below. Both mechanisms are [[Thermodynamic versus kinetic reaction control|kinetically driven]].

=== Programmed −1 ribosomal frameshifting ===
[[File:Tandem_slippage_model.jpg|thumb|Tandem slippage of 2 tRNAs at rous sarcoma virus slippery sequence. After the frameshift, new base pairings are correct at the first and second nucleotides but incorrect at wobble position. [[E-site|E]], [[P-site|P]], and [[A-site|A]] sites of the ribosome are indicated. Location of growing polypeptide chain is not indicated in image because there is not yet consensus on whether the −1 slip occurs before or after polypeptide is transferred from P-site tRNA to A-site tRNA (in this case from the Asn tRNA to the Leu tRNA).<ref name=":6" /> ]]
In −1 frameshifting, the ribosome slips back one nucleotide and continues translation in the −1 frame. There are typically three elements that comprise a −1 frameshift signal: a [[slippery sequence]], a spacer region, and an [[Nucleic acid secondary structure|RNA secondary structure.]] The slippery sequence fits a X_XXY_YYH motif, where XXX is any three identical nucleotides (though some exceptions occur), YYY typically represents UUU or AAA, and H is A, C or U. Because the structure of this motif contains 2 adjacent 3-nucleotide repeats it is believed that −1 frameshifting is described by a tandem slippage model, in which the ribosomal P-site tRNA anticodon re-pairs from XXY to XXX and the A-site anticodon re-pairs from YYH to YYY simultaneously. These new pairings are identical to the 0-frame pairings except at their third positions. This difference does not significantly disfavor anticodon binding because the third nucleotide in a codon, known as the [[Wobble base pair|wobble position]], has weaker tRNA anticodon binding specificity than the first and second nucleotides.<ref name=":02" /><ref>{{cite journal | vauthors = Crick FH | title = Codon—anticodon pairing: the wobble hypothesis | journal = Journal of Molecular Biology | volume = 19 | issue = 2 | pages = 548–555 | date = August 1966 | pmid = 5969078 | doi = 10.1016/S0022-2836(66)80022-0 }}</ref> In this model, the motif structure is explained by the fact that the first and second positions of the anticodons must be able to pair perfectly in both the 0 and −1 frames. Therefore, nucleotides 2 and 1 must be identical, and nucleotides 3 and 2 must also be identical, leading to a required sequence of 3 identical nucleotides for each tRNA that slips.<ref name=":0">{{cite journal | vauthors = Brierley I | title = Ribosomal frameshifting viral RNAs | journal = The Journal of General Virology | volume = 76 (Pt 8) | issue = 8 | pages = 1885–1892 | date = August 1995 | pmid = 7636469 | doi = 10.1099/0022-1317-76-8-1885 | doi-access = free }}</ref>

=== +1 ribosomal frameshifting ===
[[File:+1_translational_frameshift_mechanism.jpg|thumb|+1 frameshift occurs as ribosome and P-site tRNA pause to wait for arrival of rare arginine tRNA. The A-site codon in the new frame pairs to anticodon of more common glycine tRNA, and translation continues.<ref name=":5">{{cite journal | vauthors = Harger JW, Meskauskas A, Dinman JD | title = An "integrated model" of programmed ribosomal frameshifting | language = English | journal = Trends in Biochemical Sciences | volume = 27 | issue = 9 | pages = 448–454 | date = September 2002 | pmid = 12217519 | doi = 10.1016/S0968-0004(02)02149-7 | url = https://www.cell.com/trends/biochemical-sciences/abstract/S0968-0004(02)02149-7 | url-access = subscription }}</ref>]]
The slippery sequence for a +1 frameshift signal does not have the same motif, and instead appears to function by pausing the ribosome at a sequence encoding a rare amino acid.<ref name=":5" /> Ribosomes do not translate proteins at a steady rate, regardless of the sequence. Certain codons take longer to translate, because there are not equal amounts of [[tRNA]] of that particular codon in the [[cytosol]].<ref>{{cite journal | vauthors = Gurvich OL, Baranov PV, Gesteland RF, Atkins JF | title = Expression levels influence ribosomal frameshifting at the tandem rare arginine codons AGG_AGG and AGA_AGA in Escherichia coli | journal = Journal of Bacteriology | volume = 187 | issue = 12 | pages = 4023–4032 | date = June 2005 | pmid = 15937165 | pmc = 1151738 | doi = 10.1128/JB.187.12.4023-4032.2005 }}</ref> Due to this lag, there exist in small sections of codons sequences that control the rate of ribosomal frameshifting. Specifically, the ribosome must pause to wait for the arrival of a rare tRNA, and this increases the kinetic favorability of the ribosome and its associated tRNA slipping into the new frame.<ref name=":5" /><ref>{{cite journal | vauthors = Caliskan N, Katunin VI, Belardinelli R, Peske F, Rodnina MV | title = Programmed −1 frameshifting by kinetic partitioning during impeded translocation | journal = Cell | volume = 157 | issue = 7 | pages = 1619–1631 | date = June 2014 | pmid = 24949973 | doi = 10.1016/j.cell.2014.04.041 | pmc = 7112342 | doi-access = free }}</ref> In this model, the change in reading frame is caused by a single tRNA slip rather than two.

== Controlling mechanisms ==
Ribosomal frameshifting may be controlled by mechanisms found in the mRNA sequence (cis-acting). This generally refers to a slippery sequence, an RNA secondary structure, or both. A −1 frameshift signal consists of both elements separated by a spacer region typically 5–9 nucleotides long.<ref name=":02" /> Frameshifting may also be induced by other molecules which interact with the ribosome or the mRNA (trans-acting).

=== Frameshift signal elements ===
[[File:RNA_structure.001.jpg|thumb|This is a graphical representation of the HIV1 frameshift signal. A −1 frameshift in the slippery sequence region results in translation of the ''pol'' instead of the ''gag'' protein-coding region, or open reading frame (ORF). Both gag and pol proteins are required for reverse transcriptase, which is essential to HIV1 replication.<ref name=":4" /> ]]

==== Slippery sequence ====
[[Slippery sequence]]s can potentially make the reading ribosome "slip" and skip a number of [[nucleotides]] (usually only 1) and read a completely different frame thereafter. In programmed −1 ribosomal frameshifting, the slippery sequence fits a X_XXY_YYH motif, where XXX is any three identical nucleotides (though some exceptions occur), YYY typically represents UUU or AAA, and H is A, C or U. In the case of +1 frameshifting, the slippery sequence contains codons for which the corresponding tRNA is more rare, and the frameshift is favored because the codon in the new frame has a more common associated tRNA.<ref name=":5" /> One example of a slippery sequence is the [[Polyadenylation|polyA]] on mRNA, which is known to induce ribosome slippage even in the absence of any other elements.<ref>{{cite journal | vauthors = Arthur L, Pavlovic-Djuranovic S, Smith-Koutmou K, Green R, Szczesny P, Djuranovic S | title = Translational control by lysine-encoding A-rich sequences | journal = Science Advances | volume = 1 | issue = 6 | article-number = e1500154 | date = July 2015 | pmid = 26322332 | pmc = 4552401 | doi = 10.1126/sciadv.1500154 | bibcode = 2015SciA....1E0154A }}</ref>

==== RNA secondary structure ====
Efficient ribosomal frameshifting generally requires the presence of an RNA secondary structure to enhance the effects of the slippery sequence.<ref name=":0" /> The RNA structure (which can be a [[stem-loop]] or [[pseudoknot]]) is thought to pause the ribosome on the slippery site during translation, forcing it to relocate and continue replication from the −1 position. It is believed that this occurs because the structure physically blocks movement of the ribosome by becoming stuck in the ribosome mRNA tunnel.<ref name=":02" /> This model is supported by the fact that strength of the pseudoknot has been positively correlated with the level of frameshifting for associated mRNA.<ref name=":1" /><ref>{{cite journal | vauthors = Hansen TM, Reihani SN, Oddershede LB, Sørensen MA | title = Correlation between mechanical strength of messenger RNA pseudoknots and ribosomal frameshifting | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 14 | pages = 5830–5835 | date = April 2007 | pmid = 17389398 | pmc = 1838403 | doi = 10.1073/pnas.0608668104 | bibcode = 2007PNAS..104.5830H | doi-access = free }}</ref>

Below are examples of predicted secondary structures for frameshift elements shown to stimulate frameshifting in a variety of organisms. The majority of the structures shown are stem-loops, with the exception of the ALIL (apical loop-internal loop) pseudoknot structure. In these images, the larger and incomplete circles of mRNA represent linear regions. The secondary "stem-loop" structures, where "stems" are formed by a region of mRNA base pairing with another region on the same strand, are shown protruding from the linear DNA. The linear region of the HIV ribosomal frameshift signal contains a highly conserved UUU UUU A slippery sequence; many of the other predicted structures contain candidates for slippery sequences as well.

The mRNA sequences in the images can be read according to a set of guidelines. While A, T, C, and G represent a particular nucleotide at a position, there are also letters that represent ambiguity which are used when more than one kind of nucleotide could occur at that position. The rules of the International Union of Pure and Applied Chemistry ([[IUPAC]]) are as follows:<ref name="iupac" />
{| class="wikitable" style="margin-left:25px; margin-top:0px; text-align:center;"
! Symbol<ref name="iupac">{{cite web|url=http://www.chem.qmul.ac.uk/iubmb/misc/naseq.html|title=Nomenclature for Incompletely Specified Bases in Nucleic Acid Sequences|author=Nomenclature Committee of the International Union of Biochemistry (NC-IUB)|year=1984|access-date=2008-02-04}}</ref>
! Description
! colspan="5" | Bases represented
! Complement
|-
|'''A'''
| align="left" |[[Adenine|'''A'''denine]]
|A
|
|
|
| rowspan="5" |1
|T
|-
|'''C'''
| align="left" |[[Cytosine|'''C'''ytosine]]
|
|C
|
|
|G
|-
|'''G'''
| align="left" |[[Guanine|'''G'''uanine]]
|
|
|G
|
|C
|-
|'''T'''
| align="left" |[[Thymine|'''T'''hymine]]
|
|
|
|T
|A
|-
|'''U'''
| align="left" |[[Uracil|'''U'''racil]]
|
|
|
|U
|A
|- bgcolor="#e8e8e8"
|'''W'''
| align="left" |'''W'''eak
|A
|
|
|T
| rowspan="6" |2
|W
|- bgcolor="#e8e8e8"
|'''S'''
| align="left" |'''S'''trong
|
|C
|G
|
|S
|- bgcolor="#e8e8e8"
|'''M'''
| align="left" |[[Amine|a'''M'''ino]]
|A
|C
|
|
|K
|- bgcolor="#e8e8e8"
|'''K'''
| align="left" |[[Ketone|'''K'''eto]]
|
|
|G
|T
|M
|- bgcolor="#e8e8e8"
|'''R'''
| align="left" |[[Purine|pu'''R'''ine]]
|A
|
|G
|
|R
|- bgcolor="#e8e8e8"
|'''Y'''
| align="left" |[[Pyrimidine|p'''Y'''rimidine]]
|
|C
|
|T
|Y
|-
|'''B'''
| align="left" |not A ('''B''' comes after A)
|
|C
|G
|T
| rowspan="4" |3
|V
|-
|'''D'''
| align="left" |not C ('''D''' comes after C)
|A
|
|G
|T
|H
|-
|'''H'''
| align="left" |not G ('''H''' comes after G)
|A
|C
|
|T
|D
|-
|'''V'''
| align="left" |not T ('''V''' comes after T and U)
|A
|C
|G
|
|B
|- bgcolor="#e8e8e8"
|'''N'''
| align="left" |any '''N'''ucleotide (not a gap)
|A
|C
|G
|T
|4
|N
|-
|'''Z'''
| align="left" |[[0|'''Z'''ero]]
|
|
|
|
|0
|Z
|}

These symbols are also valid for RNA, except with U (uracil) replacing T (thymine).<ref name="iupac" />
{{Navbox
 | name=hide the gallery
 | title=Gallery of secondary structure images
 | titlestyle=background:#e7dcc3
 | state=autocollapse
 | list1=<gallery>
Image:ALIL pk.png | [[ALIL pseudoknot]]
Image:RF00381.jpg | [[Antizyme RNA frameshifting stimulation element]]
Image:RF00507.jpg | [[Coronavirus frameshifting stimulation element]]
Image:RF00382.jpg | [[DnaX ribosomal frameshifting element]]
Image:RF00480.jpg | [[HIV ribosomal frameshift signal]]
Image:RF00383.jpg | [[Insertion sequence IS1222 ribosomal frameshifting element]]
Image:RF_site1 secondary structure.jpg | '''RF_site1''':  Secondary structure taken from the [http://rfam.sanger.ac.uk Rfam] database. Family [http://rfam.sanger.ac.uk/family/RF01074 RF01074]. Derived from Pseudobase [http://www.ekevanbatenburg.nl/PKBASE/PKB00046.HTML PKB00046][http://www.ekevanbatenburg.nl/PKBASE/PKB00044.HTML PKB00044][http://www.ekevanbatenburg.nl/PKBASE/PKB00240.HTML PKB00240]
Image:RF_site2 secondary structure.jpg | '''RF_site2''':  Secondary structure taken from the [http://rfam.sanger.ac.uk Rfam] database. Family [http://rfam.sanger.ac.uk/family/RF01076 RF01076]. Derived from Pseudobase [http://www.ekevanbatenburg.nl/PKBASE/PKB00218.HTML PKB00218][http://www.ekevanbatenburg.nl/PKBASE/PKB00233.HTML PKB00233]
Image:RF_site3 secondary structure.jpg | '''RF_site3''':  Secondary structure taken from the [http://rfam.sanger.ac.uk Rfam] database. Family [http://rfam.sanger.ac.uk/family/RF01079 RF01079]. Derived from Pseudobase [http://www.ekevanbatenburg.nl/PKBASE/PKB00042.HTML PKB00042][http://www.ekevanbatenburg.nl/PKBASE/PKB00043.HTML PKB00043]
Image:RF_site4 secondary structure.jpg | '''RF_site4''':  Secondary structure taken from the [http://rfam.sanger.ac.uk Rfam] database. Family [http://rfam.sanger.ac.uk/family/RF01090 RF01090]. Derived from Pseudobase [http://www.ekevanbatenburg.nl/PKBASE/PKB00257.HTML PKB00257]
Image:RF_site5 secondary structure.jpg | '''RF_site5''':  Secondary structure taken from the [http://rfam.sanger.ac.uk Rfam] database. Family [http://rfam.sanger.ac.uk/family/RF01093 RF01093]. Derived from Pseudobase [http://www.ekevanbatenburg.nl/PKBASE/PKB00258.HTML PKB00258]
Image:RF_site6 secondary structure.jpg | '''RF_site6''':  Secondary structure taken from the [http://rfam.sanger.ac.uk Rfam] database. Family [http://rfam.sanger.ac.uk/family/RF01094 RF01094]. Derived from Pseudobase [http://www.ekevanbatenburg.nl/PKBASE/PKB00128.HTML PKB00128]
Image:RF_site8 secondary structure.jpg | '''RF_site8''':  Secondary structure taken from the [http://rfam.sanger.ac.uk Rfam] database. Family [http://rfam.sanger.ac.uk/family/RF01097 RF01097]. Derived from Pseudobase [http://www.ekevanbatenburg.nl/PKBASE/PKB00107.HTML PKB00107]
Image:RF_site9 secondary structure.jpg | '''RF_site9''':  Secondary structure taken from the [http://rfam.sanger.ac.uk Rfam] database. Family [http://rfam.sanger.ac.uk/family/RF01098 RF01098]. Derived from Pseudobase [http://www.ekevanbatenburg.nl/PKBASE/PKB00080.HTML PKB00080]
</gallery>
}}
{| class="wikitable sortable"
|+ Frameshift elements
! Type
! Distribution
! Ref.
|-
|[[ALIL pseudoknot]]
|[[Bacteria]]
|<ref name="pmid18474594">{{cite journal | vauthors = Mazauric MH, Licznar P, Prère MF, Canal I, Fayet O | title = Apical loop-internal loop RNA pseudoknots: a new type of stimulator of −1 translational frameshifting in bacteria | journal = The Journal of Biological Chemistry | volume = 283 | issue = 29 | pages = 20421–20432 | date = July 2008 | pmid = 18474594 | doi = 10.1074/jbc.M802829200 | doi-access = free }}</ref>
|-
|[[Antizyme RNA frameshifting stimulation element]]
|[[Invertebrate]]s
|<ref>{{cite journal | vauthors = Ivanov IP, Anderson CB, Gesteland RF, Atkins JF | title = Identification of a new antizyme mRNA +1 frameshifting stimulatory pseudoknot in a subset of diverse invertebrates and its apparent absence in intermediate species | journal = Journal of Molecular Biology | volume = 339 | issue = 3 | pages = 495–504 | date = June 2004 | pmid = 15147837 | doi = 10.1016/j.jmb.2004.03.082 | pmc = 7125782 }}</ref>
|-
|[[Coronavirus frameshifting stimulation element]]
|[[Coronavirus]]
|<ref>{{cite journal | vauthors = Baranov PV, Henderson CM, Anderson CB, Gesteland RF, Atkins JF, Howard MT | title = Programmed ribosomal frameshifting in decoding the SARS-CoV genome | journal = Virology | volume = 332 | issue = 2 | pages = 498–510 | date = February 2005 | pmid = 15680415 | doi = 10.1016/j.virol.2004.11.038 | pmc = 7111862 | doi-access = free }}</ref>
|-
|[[DnaX ribosomal frameshifting element]]
|[[Eukaryota]], [[bacteria]]
|<ref>{{cite journal | vauthors = Larsen B, Gesteland RF, Atkins JF | title = Structural probing and mutagenic analysis of the stem-loop required for Escherichia coli dnaX ribosomal frameshifting: programmed efficiency of 50% | journal = Journal of Molecular Biology | volume = 271 | issue = 1 | pages = 47–60 | date = August 1997 | pmid = 9300054 | doi = 10.1006/jmbi.1997.1162 | pmc = 7126992 }}</ref>
|-
|[[HIV ribosomal frameshift signal]]
|[[Viruses]]
|
|-
|[[Insertion sequence IS1222 ribosomal frameshifting element]]
|[[Eukaryota]], [[bacteria]]
|
|-
|Ribosomal frameshift
|[[Viruses]]
|
|}

=== Trans-acting elements ===
Small molecules, proteins, and nucleic acids have been found to stimulate levels of frameshifting. For example, the mechanism of a [[negative feedback]] loop in the [[polyamine]] synthesis pathway is based on polyamine levels stimulating an increase in +1 frameshifts, which results in production of an inhibitory [[enzyme]]. Certain proteins which are needed for codon recognition or which bind directly to the mRNA sequence have also been shown to modulate frameshifting levels. [[MicroRNA]] (miRNA) molecules may hybridize to an RNA secondary structure and affect its strength.<ref name=":3" />

== See also ==
* [[Antizyme RNA frameshifting stimulation element]]
* [[Coronavirus frameshifting stimulation element]]
* [[DnaX ribosomal frameshifting element]]
* [[Frameshift mutation]]
* [[HIV ribosomal frameshift signal]]
* [[Insertion sequence IS1222 ribosomal frameshifting element]]
* [[Recode (database)|Recode database]]
* [[Ribosomal pause]]
* [[Slippery sequence]]

== References ==
{{reflist}}

== External links ==
* {{MeshName|Frameshifting,+Ribosomal}}
* [http://www.ebi.ac.uk/Tools/Wise2/index.htm Wise2] — aligns a [[protein]] against a [[DNA]] sequence allowing [[frameshift]]s and [[intron]]s
* [http://fasta.bioch.virginia.edu/fasta_www2/fasta_www.cgi?rm=select&pgm=fy FastY] — compare a [[DNA]] sequence to a [[protein]] sequence database, allowing gaps and [[frameshift]]s
* [http://bioinfo.lifl.fr/path/ Path] {{Webarchive|url=https://web.archive.org/web/20110719124547/http://bioinfo.lifl.fr/path/ |date=19 July 2011 }} — tool that compares two [[frameshift]] [[proteins]] (back-[[Translation (genetics)|translation]] principle)
* [http://recode.ucc.ie/ Recode2] — Database of recoded genes, including those that require programmed Translational frameshift.

{{Use dmy dates|date=September 2019}}

[[Category:RNA]]
[[Category:Gene expression]]
[[Category:Cis-regulatory RNA elements]]
[[Category:Genetics]]