A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells
Long noncoding RNAs (lncRNAs) are often associated with polysomes, indicating coding potential. However, only a handful of endogenous proteins encoded by putative lncRNAs have been identified and assigned a function. Here, we report the discovery of a putative gastrointestinal-tract-specific lncRNA...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/53734 |
| _version_ | 1811253154235285504 |
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| author | Xiao Ling Li Lőrinc Pongor Wei Tang Sudipto Das Bruna R Muys Matthew F Jones Sarah B Lazar Emily A Dangelmaier Corrine CR Hartford Ioannis Grammatikakis Qinyu Hao Qinyu Sun Aaron Schetter Jennifer L Martindale BinWu Tang Lisa M Jenkins Ana I Robles Robert L Walker Stefan Ambs Raj Chari Svetlana A Shabalina Myriam Gorospe S Perwez Hussain Curtis C Harris Paul S Meltzer Kannanganattu V Prasanth Mirit I Aladjem Thorkell Andresson Ashish Lal |
| author_facet | Xiao Ling Li Lőrinc Pongor Wei Tang Sudipto Das Bruna R Muys Matthew F Jones Sarah B Lazar Emily A Dangelmaier Corrine CR Hartford Ioannis Grammatikakis Qinyu Hao Qinyu Sun Aaron Schetter Jennifer L Martindale BinWu Tang Lisa M Jenkins Ana I Robles Robert L Walker Stefan Ambs Raj Chari Svetlana A Shabalina Myriam Gorospe S Perwez Hussain Curtis C Harris Paul S Meltzer Kannanganattu V Prasanth Mirit I Aladjem Thorkell Andresson Ashish Lal |
| author_sort | Xiao Ling Li |
| collection | DOAJ |
| description | Long noncoding RNAs (lncRNAs) are often associated with polysomes, indicating coding potential. However, only a handful of endogenous proteins encoded by putative lncRNAs have been identified and assigned a function. Here, we report the discovery of a putative gastrointestinal-tract-specific lncRNA (LINC00675) that is regulated by the pioneer transcription factor FOXA1 and encodes a conserved small protein of 79 amino acids which we termed FORCP (FOXA1-Regulated Conserved Small Protein). FORCP transcript is undetectable in most cell types but is abundant in well-differentiated colorectal cancer (CRC) cells where it functions to inhibit proliferation, clonogenicity, and tumorigenesis. The epitope-tagged and endogenous FORCP protein predominantly localizes to the endoplasmic reticulum (ER). In response to ER stress, FORCP depletion results in decreased apoptosis. Our findings on the initial characterization of FORCP demonstrate that FORCP is a novel, conserved small protein encoded by a mis-annotated lncRNA that regulates apoptosis and tumorigenicity in well-differentiated CRC cells. |
| first_indexed | 2024-04-12T16:46:25Z |
| format | Article |
| id | doaj.art-c60bfdd56a884b3f80b57d44916ac23e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:46:25Z |
| publishDate | 2020-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c60bfdd56a884b3f80b57d44916ac23e2022-12-22T03:24:35ZengeLife Sciences Publications LtdeLife2050-084X2020-10-01910.7554/eLife.53734A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cellsXiao Ling Li0Lőrinc Pongor1https://orcid.org/0000-0001-5917-4628Wei Tang2Sudipto Das3Bruna R Muys4Matthew F Jones5Sarah B Lazar6Emily A Dangelmaier7https://orcid.org/0000-0002-4698-2500Corrine CR Hartford8Ioannis Grammatikakis9https://orcid.org/0000-0002-8455-1584Qinyu Hao10https://orcid.org/0000-0002-7059-7741Qinyu Sun11Aaron Schetter12Jennifer L Martindale13BinWu Tang14Lisa M Jenkins15Ana I Robles16Robert L Walker17Stefan Ambs18Raj Chari19Svetlana A Shabalina20Myriam Gorospe21S Perwez Hussain22Curtis C Harris23Paul S Meltzer24Kannanganattu V Prasanth25https://orcid.org/0000-0003-4587-8362Mirit I Aladjem26Thorkell Andresson27Ashish Lal28https://orcid.org/0000-0002-4299-8177Regulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United StatesDevelopmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, United StatesMolecular Epidemiology Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United StatesProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United StatesDepartment of Cell and Developmental Biology, Cancer Center at Illinois University of Illinois at Urbana-Champaign, Urbana, United StatesDepartment of Cell and Developmental Biology, Cancer Center at Illinois University of Illinois at Urbana-Champaign, Urbana, United StatesMolecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United StatesLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, NIH, Baltimore, United StatesLaboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, United StatesLaboratory of Cell Biology, CCR, NCI, NIH, Bethesda, United StatesMolecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United StatesMolecular Genetics Section, Genetics Branch, CCR, NCI, NIH, Bethesda, United StatesMolecular Epidemiology Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United StatesGenome Modification Core, Frederick National Lab for Cancer Research, National Cancer Institute, Frederick, United StatesNational Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, United StatesLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, NIH, Baltimore, United StatesPancreatic Cancer Unit, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United StatesMolecular Genetics and Carcinogenesis Section, Laboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, United StatesMolecular Genetics Section, Genetics Branch, CCR, NCI, NIH, Bethesda, United StatesDepartment of Cell and Developmental Biology, Cancer Center at Illinois University of Illinois at Urbana-Champaign, Urbana, United StatesDevelopmental Therapeutics Branch, CCR, NCI, NIH, Bethesda, United StatesProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, United StatesRegulatory RNAs and Cancer Section, Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, United StatesLong noncoding RNAs (lncRNAs) are often associated with polysomes, indicating coding potential. However, only a handful of endogenous proteins encoded by putative lncRNAs have been identified and assigned a function. Here, we report the discovery of a putative gastrointestinal-tract-specific lncRNA (LINC00675) that is regulated by the pioneer transcription factor FOXA1 and encodes a conserved small protein of 79 amino acids which we termed FORCP (FOXA1-Regulated Conserved Small Protein). FORCP transcript is undetectable in most cell types but is abundant in well-differentiated colorectal cancer (CRC) cells where it functions to inhibit proliferation, clonogenicity, and tumorigenesis. The epitope-tagged and endogenous FORCP protein predominantly localizes to the endoplasmic reticulum (ER). In response to ER stress, FORCP depletion results in decreased apoptosis. Our findings on the initial characterization of FORCP demonstrate that FORCP is a novel, conserved small protein encoded by a mis-annotated lncRNA that regulates apoptosis and tumorigenicity in well-differentiated CRC cells.https://elifesciences.org/articles/53734lncRNAORFFOXA1LINC00675CRCmicropeptide |
| spellingShingle | Xiao Ling Li Lőrinc Pongor Wei Tang Sudipto Das Bruna R Muys Matthew F Jones Sarah B Lazar Emily A Dangelmaier Corrine CR Hartford Ioannis Grammatikakis Qinyu Hao Qinyu Sun Aaron Schetter Jennifer L Martindale BinWu Tang Lisa M Jenkins Ana I Robles Robert L Walker Stefan Ambs Raj Chari Svetlana A Shabalina Myriam Gorospe S Perwez Hussain Curtis C Harris Paul S Meltzer Kannanganattu V Prasanth Mirit I Aladjem Thorkell Andresson Ashish Lal A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells eLife lncRNA ORF FOXA1 LINC00675 CRC micropeptide |
| title | A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells |
| title_full | A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells |
| title_fullStr | A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells |
| title_full_unstemmed | A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells |
| title_short | A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells |
| title_sort | small protein encoded by a putative lncrna regulates apoptosis and tumorigenicity in human colorectal cancer cells |
| topic | lncRNA ORF FOXA1 LINC00675 CRC micropeptide |
| url | https://elifesciences.org/articles/53734 |
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