miRNA-mediated loss of m6A increases nascent translation in glioblastoma

Within the glioblastoma cellular niche, glioma stem cells (GSCs) can give rise to differentiated glioma cells (DGCs) and, when necessary, DGCs can reciprocally give rise to GSCs to maintain the cellular equilibrium necessary for optimal tumor growth. Here, using ribosome profiling, transcriptome and...

Full description

Saved in:
Bibliographic Details
Published in:PLoS genetics 2021-03, Vol.17 (3), p.e1009086-e1009086
Main Authors: Zepecki, John P, Karambizi, David, Fajardo, J Eduardo, Snyder, Kristin M, Guetta-Terrier, Charlotte, Tang, Oliver Y, Chen, Jia-Shu, Sarkar, Atom, Fiser, Andras, Toms, Steven A, Tapinos, Nikos
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Adenosine - analogs & derivatives
Adenosine - metabolism
Base Sequence
Biology and life sciences
Brain cancer
Cell differentiation
Cell Line, Tumor
Cell self-renewal
Codons
Comparative analysis
Deoxyribonucleic acid
DNA
DNA methylation
Efficiency
Exons
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glial fibrillary acidic protein
Glioblastoma
Glioblastoma - genetics
Glioblastoma - metabolism
Humans
Medicine and Health Sciences
Methylation
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Microtubule-Associated Proteins - genetics
miRNA
N6-methyladenosine
Olig2 protein
Physical Sciences
Protein Biosynthesis
Research and Analysis Methods
RNA Interference
RNA, Messenger - genetics
Stem cells
Transcription
Transcriptome
Transplantation
Tumor Cells, Cultured
Tumorigenicity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c456t-fb70ea9a8a39093d8a4324a59aff06160daf09d8f92babae35f19222fc6d32e43
cites cdi_FETCH-LOGICAL-c456t-fb70ea9a8a39093d8a4324a59aff06160daf09d8f92babae35f19222fc6d32e43
container_end_page e1009086
container_issue 3
container_start_page e1009086
container_title PLoS genetics
container_volume 17
creator Zepecki, John P
Karambizi, David
Fajardo, J Eduardo
Snyder, Kristin M
Guetta-Terrier, Charlotte
Tang, Oliver Y
Chen, Jia-Shu
Sarkar, Atom
Fiser, Andras
Toms, Steven A
Tapinos, Nikos
description Within the glioblastoma cellular niche, glioma stem cells (GSCs) can give rise to differentiated glioma cells (DGCs) and, when necessary, DGCs can reciprocally give rise to GSCs to maintain the cellular equilibrium necessary for optimal tumor growth. Here, using ribosome profiling, transcriptome and m6A RNA sequencing, we show that GSCs from patients with different subtypes of glioblastoma share a set of transcripts, which exhibit a pattern of m6A loss and increased protein translation during differentiation. The target sequences of a group of miRNAs overlap the canonical RRACH m6A motifs of these transcripts, many of which confer a survival advantage in glioblastoma. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/ILF3/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation. Inhibition of miR-145 maintains RRACH m6A levels of CLIP3 and inhibits its nascent translation. This study highlights a critical role of miRNAs in assembling complexes for m6A demethylation and induction of protein translation during GSC state transition.
doi_str_mv 10.1371/journal.pgen.1009086
format article
fullrecord <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_2513686013</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_0007be1e0d444154b35e4996ec091839</doaj_id><sourcerecordid>2499389748</sourcerecordid><originalsourceid>FETCH-LOGICAL-c456t-fb70ea9a8a39093d8a4324a59aff06160daf09d8f92babae35f19222fc6d32e43</originalsourceid><addsrcrecordid>eNptUl1rFDEUHUSxtfoPRAd88WW2N5OPSV6EpagtlBZEn8OdmWTNkknWZFbw35vtTksrPiXknnPuvSenqt4SWBHakfNt3KeAfrXbmLAiAAqkeFadEs5p0zFgzx_dT6pXOW8BKJeqe1mdUCokK5zT6nJy327WzWRGh7MZax9zrqOtJ7GuXRiSwWxyHTAPJsz1nDBkj7OLoVTrjXex95jnOOHr6oVFn82b5Tyrfnz5_P3isrm-_Xp1sb5uBsbF3Ni-A4MKJVIFio4SGW0ZcoXWgiACRrSgRmlV22OPhnJLVNu2dhAjbQ2jZ9X7o-6ujKoXE7JuOSk7CSC0IK6OiDHiVu-SmzD90RGdvnuIaaMxzW7wRgNA1xtiYGSMEc56yg1TSpgBFJFUFa1PS7d9Xzw6mJDQPxF9Wgnup97E37pTHZG8LQIfF4EUf-1NnvXkipfeYzBxX-Yu7Wj5FCYL9MM_0P9vx46oIZWvSsY-DENAH4Jxz9KHYOglGIX27vEiD6T7JNC_SjS17g</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2513686013</pqid></control><display><type>article</type><title>miRNA-mediated loss of m6A increases nascent translation in glioblastoma</title><source>Publicly Available Content Database</source><source>PubMed Central</source><creator>Zepecki, John P ; Karambizi, David ; Fajardo, J Eduardo ; Snyder, Kristin M ; Guetta-Terrier, Charlotte ; Tang, Oliver Y ; Chen, Jia-Shu ; Sarkar, Atom ; Fiser, Andras ; Toms, Steven A ; Tapinos, Nikos</creator><contributor>Ruzov, Alexey</contributor><creatorcontrib>Zepecki, John P ; Karambizi, David ; Fajardo, J Eduardo ; Snyder, Kristin M ; Guetta-Terrier, Charlotte ; Tang, Oliver Y ; Chen, Jia-Shu ; Sarkar, Atom ; Fiser, Andras ; Toms, Steven A ; Tapinos, Nikos ; Ruzov, Alexey</creatorcontrib><description>Within the glioblastoma cellular niche, glioma stem cells (GSCs) can give rise to differentiated glioma cells (DGCs) and, when necessary, DGCs can reciprocally give rise to GSCs to maintain the cellular equilibrium necessary for optimal tumor growth. Here, using ribosome profiling, transcriptome and m6A RNA sequencing, we show that GSCs from patients with different subtypes of glioblastoma share a set of transcripts, which exhibit a pattern of m6A loss and increased protein translation during differentiation. The target sequences of a group of miRNAs overlap the canonical RRACH m6A motifs of these transcripts, many of which confer a survival advantage in glioblastoma. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/ILF3/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation. Inhibition of miR-145 maintains RRACH m6A levels of CLIP3 and inhibits its nascent translation. This study highlights a critical role of miRNAs in assembling complexes for m6A demethylation and induction of protein translation during GSC state transition.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1009086</identifier><identifier>PMID: 33684100</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>3' Untranslated Regions ; Adenosine - analogs &amp; derivatives ; Adenosine - metabolism ; Base Sequence ; Biology and life sciences ; Brain cancer ; Cell differentiation ; Cell Line, Tumor ; Cell self-renewal ; Codons ; Comparative analysis ; Deoxyribonucleic acid ; DNA ; DNA methylation ; Efficiency ; Exons ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Glial fibrillary acidic protein ; Glioblastoma ; Glioblastoma - genetics ; Glioblastoma - metabolism ; Humans ; Medicine and Health Sciences ; Methylation ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Microtubule-Associated Proteins - genetics ; miRNA ; N6-methyladenosine ; Olig2 protein ; Physical Sciences ; Protein Biosynthesis ; Research and Analysis Methods ; RNA Interference ; RNA, Messenger - genetics ; Stem cells ; Transcription ; Transcriptome ; Transplantation ; Tumor Cells, Cultured ; Tumorigenicity</subject><ispartof>PLoS genetics, 2021-03, Vol.17 (3), p.e1009086-e1009086</ispartof><rights>2021 Zepecki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Zepecki et al 2021 Zepecki et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-fb70ea9a8a39093d8a4324a59aff06160daf09d8f92babae35f19222fc6d32e43</citedby><cites>FETCH-LOGICAL-c456t-fb70ea9a8a39093d8a4324a59aff06160daf09d8f92babae35f19222fc6d32e43</cites><orcidid>0000-0003-4127-4668 ; 0000-0001-9701-8546 ; 0000-0002-6598-1837 ; 0000-0002-3265-6982 ; 0000-0001-8732-0522 ; 0000-0002-3798-5363 ; 0000-0002-8604-2708 ; 0000-0002-8164-7150 ; 0000-0003-0085-5335</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2513686013/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2513686013?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25732,27903,27904,36991,36992,44569,53770,53772,74873</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33684100$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ruzov, Alexey</contributor><creatorcontrib>Zepecki, John P</creatorcontrib><creatorcontrib>Karambizi, David</creatorcontrib><creatorcontrib>Fajardo, J Eduardo</creatorcontrib><creatorcontrib>Snyder, Kristin M</creatorcontrib><creatorcontrib>Guetta-Terrier, Charlotte</creatorcontrib><creatorcontrib>Tang, Oliver Y</creatorcontrib><creatorcontrib>Chen, Jia-Shu</creatorcontrib><creatorcontrib>Sarkar, Atom</creatorcontrib><creatorcontrib>Fiser, Andras</creatorcontrib><creatorcontrib>Toms, Steven A</creatorcontrib><creatorcontrib>Tapinos, Nikos</creatorcontrib><title>miRNA-mediated loss of m6A increases nascent translation in glioblastoma</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Within the glioblastoma cellular niche, glioma stem cells (GSCs) can give rise to differentiated glioma cells (DGCs) and, when necessary, DGCs can reciprocally give rise to GSCs to maintain the cellular equilibrium necessary for optimal tumor growth. Here, using ribosome profiling, transcriptome and m6A RNA sequencing, we show that GSCs from patients with different subtypes of glioblastoma share a set of transcripts, which exhibit a pattern of m6A loss and increased protein translation during differentiation. The target sequences of a group of miRNAs overlap the canonical RRACH m6A motifs of these transcripts, many of which confer a survival advantage in glioblastoma. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/ILF3/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation. Inhibition of miR-145 maintains RRACH m6A levels of CLIP3 and inhibits its nascent translation. This study highlights a critical role of miRNAs in assembling complexes for m6A demethylation and induction of protein translation during GSC state transition.</description><subject>3' Untranslated Regions</subject><subject>Adenosine - analogs &amp; derivatives</subject><subject>Adenosine - metabolism</subject><subject>Base Sequence</subject><subject>Biology and life sciences</subject><subject>Brain cancer</subject><subject>Cell differentiation</subject><subject>Cell Line, Tumor</subject><subject>Cell self-renewal</subject><subject>Codons</subject><subject>Comparative analysis</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Efficiency</subject><subject>Exons</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Glial fibrillary acidic protein</subject><subject>Glioblastoma</subject><subject>Glioblastoma - genetics</subject><subject>Glioblastoma - metabolism</subject><subject>Humans</subject><subject>Medicine and Health Sciences</subject><subject>Methylation</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>miRNA</subject><subject>N6-methyladenosine</subject><subject>Olig2 protein</subject><subject>Physical Sciences</subject><subject>Protein Biosynthesis</subject><subject>Research and Analysis Methods</subject><subject>RNA Interference</subject><subject>RNA, Messenger - genetics</subject><subject>Stem cells</subject><subject>Transcription</subject><subject>Transcriptome</subject><subject>Transplantation</subject><subject>Tumor Cells, Cultured</subject><subject>Tumorigenicity</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1rFDEUHUSxtfoPRAd88WW2N5OPSV6EpagtlBZEn8OdmWTNkknWZFbw35vtTksrPiXknnPuvSenqt4SWBHakfNt3KeAfrXbmLAiAAqkeFadEs5p0zFgzx_dT6pXOW8BKJeqe1mdUCokK5zT6nJy327WzWRGh7MZax9zrqOtJ7GuXRiSwWxyHTAPJsz1nDBkj7OLoVTrjXex95jnOOHr6oVFn82b5Tyrfnz5_P3isrm-_Xp1sb5uBsbF3Ni-A4MKJVIFio4SGW0ZcoXWgiACRrSgRmlV22OPhnJLVNu2dhAjbQ2jZ9X7o-6ujKoXE7JuOSk7CSC0IK6OiDHiVu-SmzD90RGdvnuIaaMxzW7wRgNA1xtiYGSMEc56yg1TSpgBFJFUFa1PS7d9Xzw6mJDQPxF9Wgnup97E37pTHZG8LQIfF4EUf-1NnvXkipfeYzBxX-Yu7Wj5FCYL9MM_0P9vx46oIZWvSsY-DENAH4Jxz9KHYOglGIX27vEiD6T7JNC_SjS17g</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Zepecki, John P</creator><creator>Karambizi, David</creator><creator>Fajardo, J Eduardo</creator><creator>Snyder, Kristin M</creator><creator>Guetta-Terrier, Charlotte</creator><creator>Tang, Oliver Y</creator><creator>Chen, Jia-Shu</creator><creator>Sarkar, Atom</creator><creator>Fiser, Andras</creator><creator>Toms, Steven A</creator><creator>Tapinos, Nikos</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-4127-4668</orcidid><orcidid>https://orcid.org/0000-0001-9701-8546</orcidid><orcidid>https://orcid.org/0000-0002-6598-1837</orcidid><orcidid>https://orcid.org/0000-0002-3265-6982</orcidid><orcidid>https://orcid.org/0000-0001-8732-0522</orcidid><orcidid>https://orcid.org/0000-0002-3798-5363</orcidid><orcidid>https://orcid.org/0000-0002-8604-2708</orcidid><orcidid>https://orcid.org/0000-0002-8164-7150</orcidid><orcidid>https://orcid.org/0000-0003-0085-5335</orcidid></search><sort><creationdate>20210301</creationdate><title>miRNA-mediated loss of m6A increases nascent translation in glioblastoma</title><author>Zepecki, John P ; Karambizi, David ; Fajardo, J Eduardo ; Snyder, Kristin M ; Guetta-Terrier, Charlotte ; Tang, Oliver Y ; Chen, Jia-Shu ; Sarkar, Atom ; Fiser, Andras ; Toms, Steven A ; Tapinos, Nikos</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-fb70ea9a8a39093d8a4324a59aff06160daf09d8f92babae35f19222fc6d32e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>3' Untranslated Regions</topic><topic>Adenosine - analogs &amp; derivatives</topic><topic>Adenosine - metabolism</topic><topic>Base Sequence</topic><topic>Biology and life sciences</topic><topic>Brain cancer</topic><topic>Cell differentiation</topic><topic>Cell Line, Tumor</topic><topic>Cell self-renewal</topic><topic>Codons</topic><topic>Comparative analysis</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>Efficiency</topic><topic>Exons</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Glial fibrillary acidic protein</topic><topic>Glioblastoma</topic><topic>Glioblastoma - genetics</topic><topic>Glioblastoma - metabolism</topic><topic>Humans</topic><topic>Medicine and Health Sciences</topic><topic>Methylation</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Microtubule-Associated Proteins - genetics</topic><topic>miRNA</topic><topic>N6-methyladenosine</topic><topic>Olig2 protein</topic><topic>Physical Sciences</topic><topic>Protein Biosynthesis</topic><topic>Research and Analysis Methods</topic><topic>RNA Interference</topic><topic>RNA, Messenger - genetics</topic><topic>Stem cells</topic><topic>Transcription</topic><topic>Transcriptome</topic><topic>Transplantation</topic><topic>Tumor Cells, Cultured</topic><topic>Tumorigenicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zepecki, John P</creatorcontrib><creatorcontrib>Karambizi, David</creatorcontrib><creatorcontrib>Fajardo, J Eduardo</creatorcontrib><creatorcontrib>Snyder, Kristin M</creatorcontrib><creatorcontrib>Guetta-Terrier, Charlotte</creatorcontrib><creatorcontrib>Tang, Oliver Y</creatorcontrib><creatorcontrib>Chen, Jia-Shu</creatorcontrib><creatorcontrib>Sarkar, Atom</creatorcontrib><creatorcontrib>Fiser, Andras</creatorcontrib><creatorcontrib>Toms, Steven A</creatorcontrib><creatorcontrib>Tapinos, Nikos</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zepecki, John P</au><au>Karambizi, David</au><au>Fajardo, J Eduardo</au><au>Snyder, Kristin M</au><au>Guetta-Terrier, Charlotte</au><au>Tang, Oliver Y</au><au>Chen, Jia-Shu</au><au>Sarkar, Atom</au><au>Fiser, Andras</au><au>Toms, Steven A</au><au>Tapinos, Nikos</au><au>Ruzov, Alexey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miRNA-mediated loss of m6A increases nascent translation in glioblastoma</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>17</volume><issue>3</issue><spage>e1009086</spage><epage>e1009086</epage><pages>e1009086-e1009086</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Within the glioblastoma cellular niche, glioma stem cells (GSCs) can give rise to differentiated glioma cells (DGCs) and, when necessary, DGCs can reciprocally give rise to GSCs to maintain the cellular equilibrium necessary for optimal tumor growth. Here, using ribosome profiling, transcriptome and m6A RNA sequencing, we show that GSCs from patients with different subtypes of glioblastoma share a set of transcripts, which exhibit a pattern of m6A loss and increased protein translation during differentiation. The target sequences of a group of miRNAs overlap the canonical RRACH m6A motifs of these transcripts, many of which confer a survival advantage in glioblastoma. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/ILF3/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation. Inhibition of miR-145 maintains RRACH m6A levels of CLIP3 and inhibits its nascent translation. This study highlights a critical role of miRNAs in assembling complexes for m6A demethylation and induction of protein translation during GSC state transition.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33684100</pmid><doi>10.1371/journal.pgen.1009086</doi><orcidid>https://orcid.org/0000-0003-4127-4668</orcidid><orcidid>https://orcid.org/0000-0001-9701-8546</orcidid><orcidid>https://orcid.org/0000-0002-6598-1837</orcidid><orcidid>https://orcid.org/0000-0002-3265-6982</orcidid><orcidid>https://orcid.org/0000-0001-8732-0522</orcidid><orcidid>https://orcid.org/0000-0002-3798-5363</orcidid><orcidid>https://orcid.org/0000-0002-8604-2708</orcidid><orcidid>https://orcid.org/0000-0002-8164-7150</orcidid><orcidid>https://orcid.org/0000-0003-0085-5335</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1553-7404
ispartof PLoS genetics, 2021-03, Vol.17 (3), p.e1009086-e1009086
issn 1553-7404
1553-7390
1553-7404
language eng
recordid cdi_plos_journals_2513686013
source Publicly Available Content Database; PubMed Central
subjects 3' Untranslated Regions
Adenosine - analogs & derivatives
Adenosine - metabolism
Base Sequence
Biology and life sciences
Brain cancer
Cell differentiation
Cell Line, Tumor
Cell self-renewal
Codons
Comparative analysis
Deoxyribonucleic acid
DNA
DNA methylation
Efficiency
Exons
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glial fibrillary acidic protein
Glioblastoma
Glioblastoma - genetics
Glioblastoma - metabolism
Humans
Medicine and Health Sciences
Methylation
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Microtubule-Associated Proteins - genetics
miRNA
N6-methyladenosine
Olig2 protein
Physical Sciences
Protein Biosynthesis
Research and Analysis Methods
RNA Interference
RNA, Messenger - genetics
Stem cells
Transcription
Transcriptome
Transplantation
Tumor Cells, Cultured
Tumorigenicity
title miRNA-mediated loss of m6A increases nascent translation in glioblastoma
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T15%3A50%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=miRNA-mediated%20loss%20of%20m6A%20increases%20nascent%20translation%20in%20glioblastoma&rft.jtitle=PLoS%20genetics&rft.au=Zepecki,%20John%20P&rft.date=2021-03-01&rft.volume=17&rft.issue=3&rft.spage=e1009086&rft.epage=e1009086&rft.pages=e1009086-e1009086&rft.issn=1553-7404&rft.eissn=1553-7404&rft_id=info:doi/10.1371/journal.pgen.1009086&rft_dat=%3Cproquest_plos_%3E2499389748%3C/proquest_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c456t-fb70ea9a8a39093d8a4324a59aff06160daf09d8f92babae35f19222fc6d32e43%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2513686013&rft_id=info:pmid/33684100&rfr_iscdi=true