A coding-independent function of gene and pseudogene mRNAs regulates tumour biology
The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of thei...
Gespeichert in:
| Veröffentlicht in: | Nature (London) 2010-06, Vol.465 (7301), p.1033-1038 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1038 |
|---|---|
| container_issue | 7301 |
| container_start_page | 1033 |
| container_title | Nature (London) |
| container_volume | 465 |
| creator | Poliseno, Laura Salmena, Leonardo Zhang, Jiangwen Carver, Brett Haveman, William J. Pandolfi, Pier Paolo |
| description | The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the
PTEN
tumour suppressor gene and its pseudogene
PTENP1
and the critical consequences of this interaction. We find that
PTENP1
is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the
PTENP1
locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic
KRAS
. We also demonstrate that the transcripts of protein-coding genes such as
PTEN
are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
A role for pseudogenes
MicroRNAs are known to regulate gene expression by interacting with incompletely complementary sequences in a target messenger RNA. But is the converse true: can mRNA expression affect the distribution of miRNAs? A new study shows that the 3′ untranslated region of a pseudogene — the tumour suppressor pseudogene
PTENP1
— can bind the same miRNAs as the related protein-coding gene,
PTEN
. This suggests that pseudogenes may have a biological function as 'decoys', sequestering miRNAs and thereby affecting their regulation of expressed genes.
The canonical role of messenger RNA (mRNA) is in protein coding and synthesis. But could mRNAs also have a role that is related to their ability to compete for microRNA binding? Here, the functional relationship between the mRNAs produced by the
PTEN
tumour suppressor gene and its pseudogene
PTENP1
is investigated. The results suggest that pseudogenes have a biological function, in sequestering microRNAs and so affecting their regulation of gene expression. |
| doi_str_mv | 10.1038/nature09144 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3206313</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>904468665</sourcerecordid><originalsourceid>FETCH-LOGICAL-c548t-b811623e9a5b0a6977fe01fbb4e7ead80324b02d7e1f351bc017a851dcbd05d63</originalsourceid><addsrcrecordid>eNqFkc1rFTEUxYMo9rW6ci-DIC509OZjksxGeJT6AUXBj3XIJHfGKTPJM5kR-t-b-p5tFcFNQrg_Ts49h5BHFF5S4PpVsMuaEFoqxB2yoULJWkit7pINANM1aC6PyHHOFwDQUCXukyMGjVIM5IZ83lYu-jEM9Rg87rAcYan6NbhljKGKfTVgwMoGX-0yrj7-es6fPmxzlXBYJ7tgrpZ1jmuqujFOcbh8QO71dsr48HCfkK9vzr6cvqvPP759f7o9r10j9FJ3mlLJOLa26cDKVqkegfZdJ1Ch9Ro4Ex0wr5D2vKGdA6qsbqh3nYfGS35CXu91d2s3o3fFebKT2aVxtunSRDuaPydh_GaG-MPwsjqnvAg8Owik-H3FvJh5zA6nyQaMazYtiJKklM1_ScW5EEBFW8gnf5EXJZpQcjCN0pxpCVfOn-8hl2LOCftr0xTMVanmVqmFfnx7z2v2d4sFeHoAbHZ26pMNbsw3HNNtQxkr3Is9l8soDJhuvP3r35-1F7rb</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>578328606</pqid></control><display><type>article</type><title>A coding-independent function of gene and pseudogene mRNAs regulates tumour biology</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature Journals Online</source><creator>Poliseno, Laura ; Salmena, Leonardo ; Zhang, Jiangwen ; Carver, Brett ; Haveman, William J. ; Pandolfi, Pier Paolo</creator><creatorcontrib>Poliseno, Laura ; Salmena, Leonardo ; Zhang, Jiangwen ; Carver, Brett ; Haveman, William J. ; Pandolfi, Pier Paolo</creatorcontrib><description>The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the
PTEN
tumour suppressor gene and its pseudogene
PTENP1
and the critical consequences of this interaction. We find that
PTENP1
is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the
PTENP1
locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic
KRAS
. We also demonstrate that the transcripts of protein-coding genes such as
PTEN
are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
A role for pseudogenes
MicroRNAs are known to regulate gene expression by interacting with incompletely complementary sequences in a target messenger RNA. But is the converse true: can mRNA expression affect the distribution of miRNAs? A new study shows that the 3′ untranslated region of a pseudogene — the tumour suppressor pseudogene
PTENP1
— can bind the same miRNAs as the related protein-coding gene,
PTEN
. This suggests that pseudogenes may have a biological function as 'decoys', sequestering miRNAs and thereby affecting their regulation of expressed genes.
The canonical role of messenger RNA (mRNA) is in protein coding and synthesis. But could mRNAs also have a role that is related to their ability to compete for microRNA binding? Here, the functional relationship between the mRNAs produced by the
PTEN
tumour suppressor gene and its pseudogene
PTENP1
is investigated. The results suggest that pseudogenes have a biological function, in sequestering microRNAs and so affecting their regulation of gene expression.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/nature09144</identifier><identifier>PMID: 20577206</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>3' Untranslated Regions - genetics ; 631/208/68 ; 631/337 ; 631/67 ; Binding sites ; Binding, Competitive ; Biological and medical sciences ; Biology ; Cancer ; Cell Line ; Gene expression ; Gene Expression Regulation, Neoplastic - genetics ; Genes, Tumor Suppressor ; Humanities and Social Sciences ; Humans ; Medical sciences ; MicroRNAs - genetics ; Models, Genetic ; multidisciplinary ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Mutation ; Neoplasms - genetics ; Protein synthesis ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins p21(ras) ; Pseudogenes - genetics ; PTEN Phosphohydrolase - genetics ; ras Proteins - genetics ; RNA, Messenger - genetics ; Rodents ; Science ; Science (multidisciplinary) ; Tumors</subject><ispartof>Nature (London), 2010-06, Vol.465 (7301), p.1033-1038</ispartof><rights>Springer Nature Limited 2010</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jun 24, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c548t-b811623e9a5b0a6977fe01fbb4e7ead80324b02d7e1f351bc017a851dcbd05d63</citedby><cites>FETCH-LOGICAL-c548t-b811623e9a5b0a6977fe01fbb4e7ead80324b02d7e1f351bc017a851dcbd05d63</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/nature09144$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nature09144$$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=22895122$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20577206$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Poliseno, Laura</creatorcontrib><creatorcontrib>Salmena, Leonardo</creatorcontrib><creatorcontrib>Zhang, Jiangwen</creatorcontrib><creatorcontrib>Carver, Brett</creatorcontrib><creatorcontrib>Haveman, William J.</creatorcontrib><creatorcontrib>Pandolfi, Pier Paolo</creatorcontrib><title>A coding-independent function of gene and pseudogene mRNAs regulates tumour biology</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the
PTEN
tumour suppressor gene and its pseudogene
PTENP1
and the critical consequences of this interaction. We find that
PTENP1
is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the
PTENP1
locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic
KRAS
. We also demonstrate that the transcripts of protein-coding genes such as
PTEN
are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
A role for pseudogenes
MicroRNAs are known to regulate gene expression by interacting with incompletely complementary sequences in a target messenger RNA. But is the converse true: can mRNA expression affect the distribution of miRNAs? A new study shows that the 3′ untranslated region of a pseudogene — the tumour suppressor pseudogene
PTENP1
— can bind the same miRNAs as the related protein-coding gene,
PTEN
. This suggests that pseudogenes may have a biological function as 'decoys', sequestering miRNAs and thereby affecting their regulation of expressed genes.
The canonical role of messenger RNA (mRNA) is in protein coding and synthesis. But could mRNAs also have a role that is related to their ability to compete for microRNA binding? Here, the functional relationship between the mRNAs produced by the
PTEN
tumour suppressor gene and its pseudogene
PTENP1
is investigated. The results suggest that pseudogenes have a biological function, in sequestering microRNAs and so affecting their regulation of gene expression.</description><subject>3' Untranslated Regions - genetics</subject><subject>631/208/68</subject><subject>631/337</subject><subject>631/67</subject><subject>Binding sites</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Biology</subject><subject>Cancer</subject><subject>Cell Line</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Genes, Tumor Suppressor</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>MicroRNAs - genetics</subject><subject>Models, Genetic</subject><subject>multidisciplinary</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Mutation</subject><subject>Neoplasms - genetics</subject><subject>Protein synthesis</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins p21(ras)</subject><subject>Pseudogenes - genetics</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>ras Proteins - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>Rodents</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Tumors</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkc1rFTEUxYMo9rW6ci-DIC509OZjksxGeJT6AUXBj3XIJHfGKTPJM5kR-t-b-p5tFcFNQrg_Ts49h5BHFF5S4PpVsMuaEFoqxB2yoULJWkit7pINANM1aC6PyHHOFwDQUCXukyMGjVIM5IZ83lYu-jEM9Rg87rAcYan6NbhljKGKfTVgwMoGX-0yrj7-es6fPmxzlXBYJ7tgrpZ1jmuqujFOcbh8QO71dsr48HCfkK9vzr6cvqvPP759f7o9r10j9FJ3mlLJOLa26cDKVqkegfZdJ1Ch9Ro4Ex0wr5D2vKGdA6qsbqh3nYfGS35CXu91d2s3o3fFebKT2aVxtunSRDuaPydh_GaG-MPwsjqnvAg8Owik-H3FvJh5zA6nyQaMazYtiJKklM1_ScW5EEBFW8gnf5EXJZpQcjCN0pxpCVfOn-8hl2LOCftr0xTMVanmVqmFfnx7z2v2d4sFeHoAbHZ26pMNbsw3HNNtQxkr3Is9l8soDJhuvP3r35-1F7rb</recordid><startdate>20100624</startdate><enddate>20100624</enddate><creator>Poliseno, Laura</creator><creator>Salmena, Leonardo</creator><creator>Zhang, Jiangwen</creator><creator>Carver, Brett</creator><creator>Haveman, William J.</creator><creator>Pandolfi, Pier Paolo</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100624</creationdate><title>A coding-independent function of gene and pseudogene mRNAs regulates tumour biology</title><author>Poliseno, Laura ; Salmena, Leonardo ; Zhang, Jiangwen ; Carver, Brett ; Haveman, William J. ; Pandolfi, Pier Paolo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c548t-b811623e9a5b0a6977fe01fbb4e7ead80324b02d7e1f351bc017a851dcbd05d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>3' Untranslated Regions - genetics</topic><topic>631/208/68</topic><topic>631/337</topic><topic>631/67</topic><topic>Binding sites</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Biology</topic><topic>Cancer</topic><topic>Cell Line</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Genes, Tumor Suppressor</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>MicroRNAs - genetics</topic><topic>Models, Genetic</topic><topic>multidisciplinary</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Mutation</topic><topic>Neoplasms - genetics</topic><topic>Protein synthesis</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins p21(ras)</topic><topic>Pseudogenes - genetics</topic><topic>PTEN Phosphohydrolase - genetics</topic><topic>ras Proteins - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>Rodents</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Poliseno, Laura</creatorcontrib><creatorcontrib>Salmena, Leonardo</creatorcontrib><creatorcontrib>Zhang, Jiangwen</creatorcontrib><creatorcontrib>Carver, Brett</creatorcontrib><creatorcontrib>Haveman, William J.</creatorcontrib><creatorcontrib>Pandolfi, Pier Paolo</creatorcontrib><collection>Pascal-Francis</collection><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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials Science Collection</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 One Psychology</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><collection>SIRS Editorial</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Poliseno, Laura</au><au>Salmena, Leonardo</au><au>Zhang, Jiangwen</au><au>Carver, Brett</au><au>Haveman, William J.</au><au>Pandolfi, Pier Paolo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A coding-independent function of gene and pseudogene mRNAs regulates tumour biology</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2010-06-24</date><risdate>2010</risdate><volume>465</volume><issue>7301</issue><spage>1033</spage><epage>1038</epage><pages>1033-1038</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the
PTEN
tumour suppressor gene and its pseudogene
PTENP1
and the critical consequences of this interaction. We find that
PTENP1
is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the
PTENP1
locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic
KRAS
. We also demonstrate that the transcripts of protein-coding genes such as
PTEN
are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
A role for pseudogenes
MicroRNAs are known to regulate gene expression by interacting with incompletely complementary sequences in a target messenger RNA. But is the converse true: can mRNA expression affect the distribution of miRNAs? A new study shows that the 3′ untranslated region of a pseudogene — the tumour suppressor pseudogene
PTENP1
— can bind the same miRNAs as the related protein-coding gene,
PTEN
. This suggests that pseudogenes may have a biological function as 'decoys', sequestering miRNAs and thereby affecting their regulation of expressed genes.
The canonical role of messenger RNA (mRNA) is in protein coding and synthesis. But could mRNAs also have a role that is related to their ability to compete for microRNA binding? Here, the functional relationship between the mRNAs produced by the
PTEN
tumour suppressor gene and its pseudogene
PTENP1
is investigated. The results suggest that pseudogenes have a biological function, in sequestering microRNAs and so affecting their regulation of gene expression.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20577206</pmid><doi>10.1038/nature09144</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 2010-06, Vol.465 (7301), p.1033-1038 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3206313 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | 3' Untranslated Regions - genetics 631/208/68 631/337 631/67 Binding sites Binding, Competitive Biological and medical sciences Biology Cancer Cell Line Gene expression Gene Expression Regulation, Neoplastic - genetics Genes, Tumor Suppressor Humanities and Social Sciences Humans Medical sciences MicroRNAs - genetics Models, Genetic multidisciplinary Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Mutation Neoplasms - genetics Protein synthesis Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins p21(ras) Pseudogenes - genetics PTEN Phosphohydrolase - genetics ras Proteins - genetics RNA, Messenger - genetics Rodents Science Science (multidisciplinary) Tumors |
| title | A coding-independent function of gene and pseudogene mRNAs regulates tumour biology |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T10%3A29%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20coding-independent%20function%20of%20gene%20and%20pseudogene%20mRNAs%20regulates%20tumour%20biology&rft.jtitle=Nature%20(London)&rft.au=Poliseno,%20Laura&rft.date=2010-06-24&rft.volume=465&rft.issue=7301&rft.spage=1033&rft.epage=1038&rft.pages=1033-1038&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/nature09144&rft_dat=%3Cproquest_pubme%3E904468665%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=578328606&rft_id=info:pmid/20577206&rfr_iscdi=true |