Vms1 and ANKZF1 peptidyl-tRNA hydrolases release nascent chains from stalled ribosomes
Ribosomal surveillance pathways scan for ribosomes that are transiently paused or terminally stalled owing to structural elements in mRNAs or nascent chain sequences 1 , 2 . Some stalls in budding yeast are sensed by the GTPase Hbs1, which loads Dom34, a catalytically inactive member of the archaeo-...
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| Veröffentlicht in: | Nature (London) 2018-05, Vol.557 (7705), p.446-451 |
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| creator | Verma, Rati Reichermeier, Kurt M. Burroughs, A. Maxwell Oania, Robert S. Reitsma, Justin M. Aravind, L. Deshaies, Raymond J. |
| description | Ribosomal surveillance pathways scan for ribosomes that are transiently paused or terminally stalled owing to structural elements in mRNAs or nascent chain sequences
1
,
2
. Some stalls in budding yeast are sensed by the GTPase Hbs1, which loads Dom34, a catalytically inactive member of the archaeo-eukaryotic release factor 1 superfamily. Hbs1–Dom34 and the ATPase Rli1 dissociate stalled ribosomes into 40S and 60S subunits. However, the 60S subunits retain the peptidyl-tRNA nascent chains, which recruit the ribosome quality control complex that consists of Rqc1–Rqc2–Ltn1–Cdc48–Ufd1–Npl4. Nascent chains ubiquitylated by the E3 ubiquitin ligase Ltn1 are extracted from the 60S subunit by the ATPase Cdc48–Ufd1–Npl4 and presented to the 26S proteasome for degradation
3
–
9
. Failure to degrade the nascent chains leads to protein aggregation and proteotoxic stress in yeast and neurodegeneration in mice
10
–
14
. Despite intensive investigations on the ribosome quality control pathway, it is not known how the tRNA is hydrolysed from the ubiquitylated nascent chain before its degradation. Here we show that the Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase. Similar to classical eukaryotic release factor 1, Vms1 activity is dependent on a conserved catalytic glutamine. Evolutionary analysis indicates that yeast Vms1 is the founding member of a clade of eukaryotic release factor 1 homologues that we designate the Vms1-like release factor 1 clade.
The Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase that cooperates with the ribosome quality control complex to catalyse the removal of nascent polypeptides from stalled ribosomes. |
| doi_str_mv | 10.1038/s41586-018-0022-5 |
| format | Article |
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1
,
2
. Some stalls in budding yeast are sensed by the GTPase Hbs1, which loads Dom34, a catalytically inactive member of the archaeo-eukaryotic release factor 1 superfamily. Hbs1–Dom34 and the ATPase Rli1 dissociate stalled ribosomes into 40S and 60S subunits. However, the 60S subunits retain the peptidyl-tRNA nascent chains, which recruit the ribosome quality control complex that consists of Rqc1–Rqc2–Ltn1–Cdc48–Ufd1–Npl4. Nascent chains ubiquitylated by the E3 ubiquitin ligase Ltn1 are extracted from the 60S subunit by the ATPase Cdc48–Ufd1–Npl4 and presented to the 26S proteasome for degradation
3
–
9
. Failure to degrade the nascent chains leads to protein aggregation and proteotoxic stress in yeast and neurodegeneration in mice
10
–
14
. Despite intensive investigations on the ribosome quality control pathway, it is not known how the tRNA is hydrolysed from the ubiquitylated nascent chain before its degradation. Here we show that the Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase. Similar to classical eukaryotic release factor 1, Vms1 activity is dependent on a conserved catalytic glutamine. Evolutionary analysis indicates that yeast Vms1 is the founding member of a clade of eukaryotic release factor 1 homologues that we designate the Vms1-like release factor 1 clade.
The Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase that cooperates with the ribosome quality control complex to catalyse the removal of nascent polypeptides from stalled ribosomes.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/s41586-018-0022-5</identifier><identifier>PMID: 29632312</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/114/2410 ; 631/337/574/1789 ; 631/80/474/1768 ; 82/1 ; 82/16 ; 82/29 ; 82/58 ; 82/80 ; 82/83 ; Adenosine triphosphatase ; ATPases ; Biodegradation ; Biopolymers ; Catalysis ; Chains ; Crystal structure ; Degradation ; Glutamine ; Guanosine triphosphatases ; Homology ; Humanities and Social Sciences ; Hydrolase ; Hydrolases ; Intelligence gathering ; Investigations ; Letter ; Ligases ; Messenger RNA ; Methods ; multidisciplinary ; Mutation ; Neurodegeneration ; Peptidyl-tRNA hydrolase ; Physiological aspects ; Polypeptides ; Proteasome 26S ; Protein interaction ; Proteins ; Quality control ; Ribosomes ; RNA ; RNA sequencing ; Science ; Science (multidisciplinary) ; Structural members ; Transfer RNA ; tRNA ; Ubiquitin ; Ubiquitin-protein ligase ; Yeast ; Yeasts</subject><ispartof>Nature (London), 2018-05, Vol.557 (7705), p.446-451</ispartof><rights>Macmillan Publishers Ltd., part of Springer Nature 2018</rights><rights>COPYRIGHT 2018 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 17, 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5335-c9b395774e702abbca1a0cf9cf19312df61c0afbaae6c2d1c00e37213ba439d13</citedby><cites>FETCH-LOGICAL-c5335-c9b395774e702abbca1a0cf9cf19312df61c0afbaae6c2d1c00e37213ba439d13</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/s41586-018-0022-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41586-018-0022-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29632312$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Verma, Rati</creatorcontrib><creatorcontrib>Reichermeier, Kurt M.</creatorcontrib><creatorcontrib>Burroughs, A. Maxwell</creatorcontrib><creatorcontrib>Oania, Robert S.</creatorcontrib><creatorcontrib>Reitsma, Justin M.</creatorcontrib><creatorcontrib>Aravind, L.</creatorcontrib><creatorcontrib>Deshaies, Raymond J.</creatorcontrib><title>Vms1 and ANKZF1 peptidyl-tRNA hydrolases release nascent chains from stalled ribosomes</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Ribosomal surveillance pathways scan for ribosomes that are transiently paused or terminally stalled owing to structural elements in mRNAs or nascent chain sequences
1
,
2
. Some stalls in budding yeast are sensed by the GTPase Hbs1, which loads Dom34, a catalytically inactive member of the archaeo-eukaryotic release factor 1 superfamily. Hbs1–Dom34 and the ATPase Rli1 dissociate stalled ribosomes into 40S and 60S subunits. However, the 60S subunits retain the peptidyl-tRNA nascent chains, which recruit the ribosome quality control complex that consists of Rqc1–Rqc2–Ltn1–Cdc48–Ufd1–Npl4. Nascent chains ubiquitylated by the E3 ubiquitin ligase Ltn1 are extracted from the 60S subunit by the ATPase Cdc48–Ufd1–Npl4 and presented to the 26S proteasome for degradation
3
–
9
. Failure to degrade the nascent chains leads to protein aggregation and proteotoxic stress in yeast and neurodegeneration in mice
10
–
14
. Despite intensive investigations on the ribosome quality control pathway, it is not known how the tRNA is hydrolysed from the ubiquitylated nascent chain before its degradation. Here we show that the Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase. Similar to classical eukaryotic release factor 1, Vms1 activity is dependent on a conserved catalytic glutamine. Evolutionary analysis indicates that yeast Vms1 is the founding member of a clade of eukaryotic release factor 1 homologues that we designate the Vms1-like release factor 1 clade.
The Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase that cooperates with the ribosome quality control complex to catalyse the removal of nascent polypeptides from stalled ribosomes.</description><subject>631/114/2410</subject><subject>631/337/574/1789</subject><subject>631/80/474/1768</subject><subject>82/1</subject><subject>82/16</subject><subject>82/29</subject><subject>82/58</subject><subject>82/80</subject><subject>82/83</subject><subject>Adenosine triphosphatase</subject><subject>ATPases</subject><subject>Biodegradation</subject><subject>Biopolymers</subject><subject>Catalysis</subject><subject>Chains</subject><subject>Crystal structure</subject><subject>Degradation</subject><subject>Glutamine</subject><subject>Guanosine triphosphatases</subject><subject>Homology</subject><subject>Humanities and Social Sciences</subject><subject>Hydrolase</subject><subject>Hydrolases</subject><subject>Intelligence gathering</subject><subject>Investigations</subject><subject>Letter</subject><subject>Ligases</subject><subject>Messenger RNA</subject><subject>Methods</subject><subject>multidisciplinary</subject><subject>Mutation</subject><subject>Neurodegeneration</subject><subject>Peptidyl-tRNA hydrolase</subject><subject>Physiological aspects</subject><subject>Polypeptides</subject><subject>Proteasome 26S</subject><subject>Protein interaction</subject><subject>Proteins</subject><subject>Quality control</subject><subject>Ribosomes</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Structural members</subject><subject>Transfer RNA</subject><subject>tRNA</subject><subject>Ubiquitin</subject><subject>Ubiquitin-protein ligase</subject><subject>Yeast</subject><subject>Yeasts</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kk9v1DAQxS0EokvhA3BBFlzoIcV_Eic5rioKFVUrFeiBi-U4k20qx07tRGK_PbPalrLVIh9sz_zm6Wn0CHnL2TFnsvqUcl5UKmO8yhgTIiuekQXPS5XlqiqfkwUWsVNJdUBepXTLGCt4mb8kB6JWUkguFuT6ekicGt_S5cW3X6ecjjBOfbt22XR1saQ36zYGZxIkGsEBPqg3yYKfqL0xvU-0i2GgaTLOQUtj34QUBkivyYvOuARv7u9D8vP084-Tr9n55Zezk-V5Zgspi8zWjayLssyhZMI0jTXcMNvVtuM12ms7xS0zXWMMKCta_DCQpeCyMbmsWy4Pycet7hjD3Qxp0kOP9pwzHsKctGAC-YrnCtEPT9DbMEeP7pAqavSjquqRWhkHuvddmKKxG1G9LEqhZI2bRyrbQ63AQzQueOh6LO_w7_fwduzv9L_Q8R4ITwtDb_eqHu0MIDPB72ll5pT02ferXZZvWRtDShE6PcZ-MHGtOdObMOltmDSGSW_CpAuceXe_sbkZoP078ZAeBMQWSNjyK4iPK_2_6h_yY88Y</recordid><startdate>20180501</startdate><enddate>20180501</enddate><creator>Verma, Rati</creator><creator>Reichermeier, Kurt M.</creator><creator>Burroughs, A. 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Maxwell</au><au>Oania, Robert S.</au><au>Reitsma, Justin M.</au><au>Aravind, L.</au><au>Deshaies, Raymond J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vms1 and ANKZF1 peptidyl-tRNA hydrolases release nascent chains from stalled ribosomes</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2018-05-01</date><risdate>2018</risdate><volume>557</volume><issue>7705</issue><spage>446</spage><epage>451</epage><pages>446-451</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><abstract>Ribosomal surveillance pathways scan for ribosomes that are transiently paused or terminally stalled owing to structural elements in mRNAs or nascent chain sequences
1
,
2
. Some stalls in budding yeast are sensed by the GTPase Hbs1, which loads Dom34, a catalytically inactive member of the archaeo-eukaryotic release factor 1 superfamily. Hbs1–Dom34 and the ATPase Rli1 dissociate stalled ribosomes into 40S and 60S subunits. However, the 60S subunits retain the peptidyl-tRNA nascent chains, which recruit the ribosome quality control complex that consists of Rqc1–Rqc2–Ltn1–Cdc48–Ufd1–Npl4. Nascent chains ubiquitylated by the E3 ubiquitin ligase Ltn1 are extracted from the 60S subunit by the ATPase Cdc48–Ufd1–Npl4 and presented to the 26S proteasome for degradation
3
–
9
. Failure to degrade the nascent chains leads to protein aggregation and proteotoxic stress in yeast and neurodegeneration in mice
10
–
14
. Despite intensive investigations on the ribosome quality control pathway, it is not known how the tRNA is hydrolysed from the ubiquitylated nascent chain before its degradation. Here we show that the Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase. Similar to classical eukaryotic release factor 1, Vms1 activity is dependent on a conserved catalytic glutamine. Evolutionary analysis indicates that yeast Vms1 is the founding member of a clade of eukaryotic release factor 1 homologues that we designate the Vms1-like release factor 1 clade.
The Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase that cooperates with the ribosome quality control complex to catalyse the removal of nascent polypeptides from stalled ribosomes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29632312</pmid><doi>10.1038/s41586-018-0022-5</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 2018-05, Vol.557 (7705), p.446-451 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2023728146 |
| source | Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | 631/114/2410 631/337/574/1789 631/80/474/1768 82/1 82/16 82/29 82/58 82/80 82/83 Adenosine triphosphatase ATPases Biodegradation Biopolymers Catalysis Chains Crystal structure Degradation Glutamine Guanosine triphosphatases Homology Humanities and Social Sciences Hydrolase Hydrolases Intelligence gathering Investigations Letter Ligases Messenger RNA Methods multidisciplinary Mutation Neurodegeneration Peptidyl-tRNA hydrolase Physiological aspects Polypeptides Proteasome 26S Protein interaction Proteins Quality control Ribosomes RNA RNA sequencing Science Science (multidisciplinary) Structural members Transfer RNA tRNA Ubiquitin Ubiquitin-protein ligase Yeast Yeasts |
| title | Vms1 and ANKZF1 peptidyl-tRNA hydrolases release nascent chains from stalled ribosomes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T18%3A01%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Vms1%20and%20ANKZF1%20peptidyl-tRNA%20hydrolases%20release%20nascent%20chains%20from%20stalled%20ribosomes&rft.jtitle=Nature%20(London)&rft.au=Verma,%20Rati&rft.date=2018-05-01&rft.volume=557&rft.issue=7705&rft.spage=446&rft.epage=451&rft.pages=446-451&rft.issn=0028-0836&rft.eissn=1476-4687&rft_id=info:doi/10.1038/s41586-018-0022-5&rft_dat=%3Cgale_proqu%3EA572639103%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2059533688&rft_id=info:pmid/29632312&rft_galeid=A572639103&rfr_iscdi=true |