A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting
Tying the pseudoknot Ribosomal frameshifting is a translational mechanism involved in protein synthesis during the replication of many viral pathogens and in cellular genes more generally. A new set of images of an 80S ribosome stalled at an mRNA pseudoknot shows how the pseudoknot manipulates the r...
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| Veröffentlicht in: | Nature 2006-05, Vol.441 (7090), p.244-247 |
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| creator | Namy, Olivier Moran, Stephen J. Stuart, David I. Gilbert, Robert J. C. Brierley, Ian |
| description | Tying the pseudoknot
Ribosomal frameshifting is a translational mechanism involved in protein synthesis during the replication of many viral pathogens and in cellular genes more generally. A new set of images of an 80S ribosome stalled at an mRNA pseudoknot shows how the pseudoknot manipulates the ribosome into a different reading frame.
Cryoelectron microscopic imaging is used to visualize a translating ribosome stalled during frameshifting.
The triplet-based genetic code requires that translating ribosomes maintain the reading frame of a messenger RNA faithfully to ensure correct protein synthesis
1
. However, in programmed -1 ribosomal frameshifting
2
, a specific subversion of frame maintenance takes place, wherein the ribosome is forced to shift one nucleotide backwards into an overlapping reading frame and to translate an entirely new sequence of amino acids. This process is indispensable in the replication of numerous viral pathogens, including HIV and the coronavirus associated with severe acute respiratory syndrome
3
, and is also exploited in the expression of several cellular genes
4
. Frameshifting is promoted by an mRNA signal composed of two essential elements: a heptanucleotide ‘slippery’ sequence
5
and an adjacent mRNA secondary structure, most often an mRNA pseudoknot
6
. How these components operate together to manipulate the ribosome is unknown. Here we describe the observation of a ribosome–mRNA pseudoknot complex that is stalled in the process of -1 frameshifting. Cryoelectron microscopic imaging of purified mammalian 80S ribosomes from rabbit reticulocytes paused at a coronavirus pseudoknot reveals an intermediate of the frameshifting process. From this it can be seen how the pseudoknot interacts with the ribosome to block the mRNA entrance channel, compromising the translocation process and leading to a spring-like deformation of the P-site transfer RNA. In addition, we identify movements of the likely eukaryotic ribosomal helicase and confirm a direct interaction between the translocase eEF2 and the P-site tRNA. Together, the structural changes provide a mechanical explanation of how the pseudoknot manipulates the ribosome into a different reading frame. |
| doi_str_mv | 10.1038/nature04735 |
| format | Article |
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Ribosomal frameshifting is a translational mechanism involved in protein synthesis during the replication of many viral pathogens and in cellular genes more generally. A new set of images of an 80S ribosome stalled at an mRNA pseudoknot shows how the pseudoknot manipulates the ribosome into a different reading frame.
Cryoelectron microscopic imaging is used to visualize a translating ribosome stalled during frameshifting.
The triplet-based genetic code requires that translating ribosomes maintain the reading frame of a messenger RNA faithfully to ensure correct protein synthesis
1
. However, in programmed -1 ribosomal frameshifting
2
, a specific subversion of frame maintenance takes place, wherein the ribosome is forced to shift one nucleotide backwards into an overlapping reading frame and to translate an entirely new sequence of amino acids. This process is indispensable in the replication of numerous viral pathogens, including HIV and the coronavirus associated with severe acute respiratory syndrome
3
, and is also exploited in the expression of several cellular genes
4
. Frameshifting is promoted by an mRNA signal composed of two essential elements: a heptanucleotide ‘slippery’ sequence
5
and an adjacent mRNA secondary structure, most often an mRNA pseudoknot
6
. How these components operate together to manipulate the ribosome is unknown. Here we describe the observation of a ribosome–mRNA pseudoknot complex that is stalled in the process of -1 frameshifting. Cryoelectron microscopic imaging of purified mammalian 80S ribosomes from rabbit reticulocytes paused at a coronavirus pseudoknot reveals an intermediate of the frameshifting process. From this it can be seen how the pseudoknot interacts with the ribosome to block the mRNA entrance channel, compromising the translocation process and leading to a spring-like deformation of the P-site transfer RNA. In addition, we identify movements of the likely eukaryotic ribosomal helicase and confirm a direct interaction between the translocase eEF2 and the P-site tRNA. Together, the structural changes provide a mechanical explanation of how the pseudoknot manipulates the ribosome into a different reading frame.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/nature04735</identifier><identifier>PMID: 16688178</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Amino acids ; Animals ; Biochemistry, Molecular Biology ; Biological and medical sciences ; Coronavirus - genetics ; COVID-19 ; Deformation ; Frameshift Mutation - genetics ; Frameshifting, Ribosomal - physiology ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Genetics ; Genomics ; HIV ; Human immunodeficiency virus ; Humanities and Social Sciences ; letter ; Life Sciences ; Mammals ; Methods ; Models, Biological ; Models, Molecular ; Molecular and cellular biology ; Molecular genetics ; Movement ; multidisciplinary ; Nucleic Acid Conformation ; Pathogens ; Protein biosynthesis ; Protein synthesis ; Rabbits ; Ribonucleic acid ; Ribosomes - chemistry ; Ribosomes - genetics ; Ribosomes - metabolism ; RNA ; RNA, Messenger - chemistry ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA, Transfer - chemistry ; RNA, Transfer - genetics ; RNA, Transfer - metabolism ; SARS coronavirus ; Science ; Science (multidisciplinary) ; Severe acute respiratory syndrome ; Signal transduction ; Translation. Translation factors. Protein processing ; Translocation</subject><ispartof>Nature, 2006-05, Vol.441 (7090), p.244-247</ispartof><rights>Springer Nature Limited 2006</rights><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 11, 2006</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Nature Publishing Group 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1014t-a165b326560c4ffef02fc7e824bdc9ad7c2085cef8efeb9a982b91af5977fba93</citedby><cites>FETCH-LOGICAL-c1014t-a165b326560c4ffef02fc7e824bdc9ad7c2085cef8efeb9a982b91af5977fba93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nature04735$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nature04735$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17741485$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16688178$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00079598$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Namy, Olivier</creatorcontrib><creatorcontrib>Moran, Stephen J.</creatorcontrib><creatorcontrib>Stuart, David I.</creatorcontrib><creatorcontrib>Gilbert, Robert J. C.</creatorcontrib><creatorcontrib>Brierley, Ian</creatorcontrib><title>A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting</title><title>Nature</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Tying the pseudoknot
Ribosomal frameshifting is a translational mechanism involved in protein synthesis during the replication of many viral pathogens and in cellular genes more generally. A new set of images of an 80S ribosome stalled at an mRNA pseudoknot shows how the pseudoknot manipulates the ribosome into a different reading frame.
Cryoelectron microscopic imaging is used to visualize a translating ribosome stalled during frameshifting.
The triplet-based genetic code requires that translating ribosomes maintain the reading frame of a messenger RNA faithfully to ensure correct protein synthesis
1
. However, in programmed -1 ribosomal frameshifting
2
, a specific subversion of frame maintenance takes place, wherein the ribosome is forced to shift one nucleotide backwards into an overlapping reading frame and to translate an entirely new sequence of amino acids. This process is indispensable in the replication of numerous viral pathogens, including HIV and the coronavirus associated with severe acute respiratory syndrome
3
, and is also exploited in the expression of several cellular genes
4
. Frameshifting is promoted by an mRNA signal composed of two essential elements: a heptanucleotide ‘slippery’ sequence
5
and an adjacent mRNA secondary structure, most often an mRNA pseudoknot
6
. How these components operate together to manipulate the ribosome is unknown. Here we describe the observation of a ribosome–mRNA pseudoknot complex that is stalled in the process of -1 frameshifting. Cryoelectron microscopic imaging of purified mammalian 80S ribosomes from rabbit reticulocytes paused at a coronavirus pseudoknot reveals an intermediate of the frameshifting process. From this it can be seen how the pseudoknot interacts with the ribosome to block the mRNA entrance channel, compromising the translocation process and leading to a spring-like deformation of the P-site transfer RNA. In addition, we identify movements of the likely eukaryotic ribosomal helicase and confirm a direct interaction between the translocase eEF2 and the P-site tRNA. Together, the structural changes provide a mechanical explanation of how the pseudoknot manipulates the ribosome into a different reading frame.</description><subject>Amino acids</subject><subject>Animals</subject><subject>Biochemistry, Molecular Biology</subject><subject>Biological and medical sciences</subject><subject>Coronavirus - genetics</subject><subject>COVID-19</subject><subject>Deformation</subject><subject>Frameshift Mutation - genetics</subject><subject>Frameshifting, Ribosomal - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Genetics</subject><subject>Genomics</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humanities and Social Sciences</subject><subject>letter</subject><subject>Life Sciences</subject><subject>Mammals</subject><subject>Methods</subject><subject>Models, Biological</subject><subject>Models, Molecular</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Movement</subject><subject>multidisciplinary</subject><subject>Nucleic Acid Conformation</subject><subject>Pathogens</subject><subject>Protein biosynthesis</subject><subject>Protein synthesis</subject><subject>Rabbits</subject><subject>Ribonucleic acid</subject><subject>Ribosomes - chemistry</subject><subject>Ribosomes - genetics</subject><subject>Ribosomes - metabolism</subject><subject>RNA</subject><subject>RNA, Messenger - chemistry</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Transfer - chemistry</subject><subject>RNA, Transfer - genetics</subject><subject>RNA, Transfer - metabolism</subject><subject>SARS coronavirus</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Severe acute respiratory syndrome</subject><subject>Signal transduction</subject><subject>Translation. Translation factors. 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C. ; Brierley, Ian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1014t-a165b326560c4ffef02fc7e824bdc9ad7c2085cef8efeb9a982b91af5977fba93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Amino acids</topic><topic>Animals</topic><topic>Biochemistry, Molecular Biology</topic><topic>Biological and medical sciences</topic><topic>Coronavirus - genetics</topic><topic>COVID-19</topic><topic>Deformation</topic><topic>Frameshift Mutation - genetics</topic><topic>Frameshifting, Ribosomal - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Genetics</topic><topic>Genomics</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Humanities and Social Sciences</topic><topic>letter</topic><topic>Life Sciences</topic><topic>Mammals</topic><topic>Methods</topic><topic>Models, Biological</topic><topic>Models, Molecular</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Movement</topic><topic>multidisciplinary</topic><topic>Nucleic Acid Conformation</topic><topic>Pathogens</topic><topic>Protein biosynthesis</topic><topic>Protein synthesis</topic><topic>Rabbits</topic><topic>Ribonucleic acid</topic><topic>Ribosomes - chemistry</topic><topic>Ribosomes - genetics</topic><topic>Ribosomes - metabolism</topic><topic>RNA</topic><topic>RNA, Messenger - chemistry</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Transfer - chemistry</topic><topic>RNA, Transfer - genetics</topic><topic>RNA, Transfer - metabolism</topic><topic>SARS coronavirus</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Severe acute respiratory syndrome</topic><topic>Signal transduction</topic><topic>Translation. 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Namy, Olivier</au><au>Moran, Stephen J.</au><au>Stuart, David I.</au><au>Gilbert, Robert J. C.</au><au>Brierley, Ian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting</atitle><jtitle>Nature</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2006-05-11</date><risdate>2006</risdate><volume>441</volume><issue>7090</issue><spage>244</spage><epage>247</epage><pages>244-247</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><eissn>1476-4679</eissn><coden>NATUAS</coden><abstract>Tying the pseudoknot
Ribosomal frameshifting is a translational mechanism involved in protein synthesis during the replication of many viral pathogens and in cellular genes more generally. A new set of images of an 80S ribosome stalled at an mRNA pseudoknot shows how the pseudoknot manipulates the ribosome into a different reading frame.
Cryoelectron microscopic imaging is used to visualize a translating ribosome stalled during frameshifting.
The triplet-based genetic code requires that translating ribosomes maintain the reading frame of a messenger RNA faithfully to ensure correct protein synthesis
1
. However, in programmed -1 ribosomal frameshifting
2
, a specific subversion of frame maintenance takes place, wherein the ribosome is forced to shift one nucleotide backwards into an overlapping reading frame and to translate an entirely new sequence of amino acids. This process is indispensable in the replication of numerous viral pathogens, including HIV and the coronavirus associated with severe acute respiratory syndrome
3
, and is also exploited in the expression of several cellular genes
4
. Frameshifting is promoted by an mRNA signal composed of two essential elements: a heptanucleotide ‘slippery’ sequence
5
and an adjacent mRNA secondary structure, most often an mRNA pseudoknot
6
. How these components operate together to manipulate the ribosome is unknown. Here we describe the observation of a ribosome–mRNA pseudoknot complex that is stalled in the process of -1 frameshifting. Cryoelectron microscopic imaging of purified mammalian 80S ribosomes from rabbit reticulocytes paused at a coronavirus pseudoknot reveals an intermediate of the frameshifting process. From this it can be seen how the pseudoknot interacts with the ribosome to block the mRNA entrance channel, compromising the translocation process and leading to a spring-like deformation of the P-site transfer RNA. In addition, we identify movements of the likely eukaryotic ribosomal helicase and confirm a direct interaction between the translocase eEF2 and the P-site tRNA. Together, the structural changes provide a mechanical explanation of how the pseudoknot manipulates the ribosome into a different reading frame.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16688178</pmid><doi>10.1038/nature04735</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature, 2006-05, Vol.441 (7090), p.244-247 |
| issn | 0028-0836 1476-4687 1476-4679 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7094908 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Amino acids Animals Biochemistry, Molecular Biology Biological and medical sciences Coronavirus - genetics COVID-19 Deformation Frameshift Mutation - genetics Frameshifting, Ribosomal - physiology Fundamental and applied biological sciences. Psychology Gene expression Genetics Genomics HIV Human immunodeficiency virus Humanities and Social Sciences letter Life Sciences Mammals Methods Models, Biological Models, Molecular Molecular and cellular biology Molecular genetics Movement multidisciplinary Nucleic Acid Conformation Pathogens Protein biosynthesis Protein synthesis Rabbits Ribonucleic acid Ribosomes - chemistry Ribosomes - genetics Ribosomes - metabolism RNA RNA, Messenger - chemistry RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Transfer - chemistry RNA, Transfer - genetics RNA, Transfer - metabolism SARS coronavirus Science Science (multidisciplinary) Severe acute respiratory syndrome Signal transduction Translation. Translation factors. Protein processing Translocation |
| title | A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T20%3A51%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20mechanical%20explanation%20of%20RNA%20pseudoknot%20function%20in%20programmed%20ribosomal%20frameshifting&rft.jtitle=Nature&rft.au=Namy,%20Olivier&rft.date=2006-05-11&rft.volume=441&rft.issue=7090&rft.spage=244&rft.epage=247&rft.pages=244-247&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/nature04735&rft_dat=%3Cgale_pubme%3EA185450337%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=204546195&rft_id=info:pmid/16688178&rft_galeid=A185450337&rfr_iscdi=true |