Differential processing of small RNAs during endoplasmic reticulum stress
The accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen due to the disruption of the homeostatic system of the ER leads to the induction of the ER stress response. Cellular stress-induced pathways globally transform genes expression on both the transcriptional and post-transcr...
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| Veröffentlicht in: | Scientific reports 2017-04, Vol.7 (1), p.46080-46080, Article 46080 |
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| creator | Mesitov, Mikhail V. Soldatov, Ruslan A. Zaichenko, Danila M. Malakho, Sophie G. Klementyeva, Tatyana S. Sokolovskaya, Alisa A. Kubatiev, Aslan A. Mironov, Andrey A. Moskovtsev, Aleksey A. |
| description | The accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen due to the disruption of the homeostatic system of the ER leads to the induction of the ER stress response. Cellular stress-induced pathways globally transform genes expression on both the transcriptional and post-transcriptional levels with small RNA involvement as regulators of the stress response. The modulation of small RNA processing might represent an additional layer of a complex stress response program. However, it is poorly understood. Here, we studied changes in expression and small RNAs processing upon ER stress in Jurkat T-cells. Induced by ER-stress, depletion of miRNAs among small RNA composition was accompanied by a global decrease of 3′ mono-adenylated, mono-cytodinylated and a global increase of 3′ mono-uridinylated miRNA isoforms. We observed the specific subset of differentially expressed microRNAs, and also the dramatic induction of 32-nt tRNA fragments precisely phased to 5′ and 3′ ends of tRNA from a subset of tRNA isotypes. The induction of these tRNA fragments was linked to Angiogenin RNase, which mediates translation inhibition. Overall, the global perturbations of the expression and processing of miRNAs and tiRNAs were the most prominent features of small RNA transcriptome changes upon ER stress. |
| doi_str_mv | 10.1038/srep46080 |
| format | Article |
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Cellular stress-induced pathways globally transform genes expression on both the transcriptional and post-transcriptional levels with small RNA involvement as regulators of the stress response. The modulation of small RNA processing might represent an additional layer of a complex stress response program. However, it is poorly understood. Here, we studied changes in expression and small RNAs processing upon ER stress in Jurkat T-cells. Induced by ER-stress, depletion of miRNAs among small RNA composition was accompanied by a global decrease of 3′ mono-adenylated, mono-cytodinylated and a global increase of 3′ mono-uridinylated miRNA isoforms. We observed the specific subset of differentially expressed microRNAs, and also the dramatic induction of 32-nt tRNA fragments precisely phased to 5′ and 3′ ends of tRNA from a subset of tRNA isotypes. The induction of these tRNA fragments was linked to Angiogenin RNase, which mediates translation inhibition. Overall, the global perturbations of the expression and processing of miRNAs and tiRNAs were the most prominent features of small RNA transcriptome changes upon ER stress.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep46080</identifier><identifier>PMID: 28452371</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38/77 ; 631/114/2391 ; 631/337/384/521 ; Angiogenin ; Base Sequence ; Cellular stress response ; Dithiothreitol - pharmacology ; Endoplasmic reticulum ; Endoplasmic Reticulum Stress - drug effects ; Endoplasmic Reticulum Stress - genetics ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Library ; Humanities and Social Sciences ; Humans ; Isoforms ; Isotypes ; Jurkat Cells ; Lymphocytes T ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Molecular Sequence Annotation ; multidisciplinary ; Nucleic Acid Conformation ; Nucleotides - genetics ; Post-transcription ; Protein folding ; Ribonuclease ; RNA processing ; RNA Processing, Post-Transcriptional - drug effects ; RNA Processing, Post-Transcriptional - genetics ; RNA, Transfer - chemistry ; RNA, Transfer - genetics ; RNA, Transfer - metabolism ; Science ; Stress response ; T-Lymphocytes - drug effects ; T-Lymphocytes - metabolism ; Transcription ; Transcriptome - drug effects ; Transcriptome - genetics ; tRNA</subject><ispartof>Scientific reports, 2017-04, Vol.7 (1), p.46080-46080, Article 46080</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Apr 2017</rights><rights>Copyright © 2017, The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-4e5a651c23f19c619ed9b09f018985f425cbd6c3f903edbfd0d75ccdb1e335a63</citedby><cites>FETCH-LOGICAL-c438t-4e5a651c23f19c619ed9b09f018985f425cbd6c3f903edbfd0d75ccdb1e335a63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408347/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408347/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28452371$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mesitov, Mikhail V.</creatorcontrib><creatorcontrib>Soldatov, Ruslan A.</creatorcontrib><creatorcontrib>Zaichenko, Danila M.</creatorcontrib><creatorcontrib>Malakho, Sophie G.</creatorcontrib><creatorcontrib>Klementyeva, Tatyana S.</creatorcontrib><creatorcontrib>Sokolovskaya, Alisa A.</creatorcontrib><creatorcontrib>Kubatiev, Aslan A.</creatorcontrib><creatorcontrib>Mironov, Andrey A.</creatorcontrib><creatorcontrib>Moskovtsev, Aleksey A.</creatorcontrib><title>Differential processing of small RNAs during endoplasmic reticulum stress</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen due to the disruption of the homeostatic system of the ER leads to the induction of the ER stress response. Cellular stress-induced pathways globally transform genes expression on both the transcriptional and post-transcriptional levels with small RNA involvement as regulators of the stress response. The modulation of small RNA processing might represent an additional layer of a complex stress response program. However, it is poorly understood. Here, we studied changes in expression and small RNAs processing upon ER stress in Jurkat T-cells. Induced by ER-stress, depletion of miRNAs among small RNA composition was accompanied by a global decrease of 3′ mono-adenylated, mono-cytodinylated and a global increase of 3′ mono-uridinylated miRNA isoforms. We observed the specific subset of differentially expressed microRNAs, and also the dramatic induction of 32-nt tRNA fragments precisely phased to 5′ and 3′ ends of tRNA from a subset of tRNA isotypes. The induction of these tRNA fragments was linked to Angiogenin RNase, which mediates translation inhibition. Overall, the global perturbations of the expression and processing of miRNAs and tiRNAs were the most prominent features of small RNA transcriptome changes upon ER stress.</description><subject>38/77</subject><subject>631/114/2391</subject><subject>631/337/384/521</subject><subject>Angiogenin</subject><subject>Base Sequence</subject><subject>Cellular stress response</subject><subject>Dithiothreitol - pharmacology</subject><subject>Endoplasmic reticulum</subject><subject>Endoplasmic Reticulum Stress - drug effects</subject><subject>Endoplasmic Reticulum Stress - genetics</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Library</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Isoforms</subject><subject>Isotypes</subject><subject>Jurkat Cells</subject><subject>Lymphocytes T</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - 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pharmacology</topic><topic>Endoplasmic reticulum</topic><topic>Endoplasmic Reticulum Stress - drug effects</topic><topic>Endoplasmic Reticulum Stress - genetics</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Gene Library</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Isoforms</topic><topic>Isotypes</topic><topic>Jurkat Cells</topic><topic>Lymphocytes T</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Molecular Sequence Annotation</topic><topic>multidisciplinary</topic><topic>Nucleic Acid Conformation</topic><topic>Nucleotides - genetics</topic><topic>Post-transcription</topic><topic>Protein folding</topic><topic>Ribonuclease</topic><topic>RNA processing</topic><topic>RNA Processing, Post-Transcriptional - drug effects</topic><topic>RNA Processing, Post-Transcriptional - genetics</topic><topic>RNA, Transfer - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mesitov, Mikhail V.</au><au>Soldatov, Ruslan A.</au><au>Zaichenko, Danila M.</au><au>Malakho, Sophie G.</au><au>Klementyeva, Tatyana S.</au><au>Sokolovskaya, Alisa A.</au><au>Kubatiev, Aslan A.</au><au>Mironov, Andrey A.</au><au>Moskovtsev, Aleksey A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential processing of small RNAs during endoplasmic reticulum stress</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-04-13</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>46080</spage><epage>46080</epage><pages>46080-46080</pages><artnum>46080</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen due to the disruption of the homeostatic system of the ER leads to the induction of the ER stress response. Cellular stress-induced pathways globally transform genes expression on both the transcriptional and post-transcriptional levels with small RNA involvement as regulators of the stress response. The modulation of small RNA processing might represent an additional layer of a complex stress response program. However, it is poorly understood. Here, we studied changes in expression and small RNAs processing upon ER stress in Jurkat T-cells. Induced by ER-stress, depletion of miRNAs among small RNA composition was accompanied by a global decrease of 3′ mono-adenylated, mono-cytodinylated and a global increase of 3′ mono-uridinylated miRNA isoforms. We observed the specific subset of differentially expressed microRNAs, and also the dramatic induction of 32-nt tRNA fragments precisely phased to 5′ and 3′ ends of tRNA from a subset of tRNA isotypes. The induction of these tRNA fragments was linked to Angiogenin RNase, which mediates translation inhibition. Overall, the global perturbations of the expression and processing of miRNAs and tiRNAs were the most prominent features of small RNA transcriptome changes upon ER stress.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28452371</pmid><doi>10.1038/srep46080</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 38/77 631/114/2391 631/337/384/521 Angiogenin Base Sequence Cellular stress response Dithiothreitol - pharmacology Endoplasmic reticulum Endoplasmic Reticulum Stress - drug effects Endoplasmic Reticulum Stress - genetics Gene expression Gene Expression Profiling Gene Expression Regulation, Neoplastic - drug effects Gene Library Humanities and Social Sciences Humans Isoforms Isotypes Jurkat Cells Lymphocytes T MicroRNAs - genetics MicroRNAs - metabolism miRNA Molecular Sequence Annotation multidisciplinary Nucleic Acid Conformation Nucleotides - genetics Post-transcription Protein folding Ribonuclease RNA processing RNA Processing, Post-Transcriptional - drug effects RNA Processing, Post-Transcriptional - genetics RNA, Transfer - chemistry RNA, Transfer - genetics RNA, Transfer - metabolism Science Stress response T-Lymphocytes - drug effects T-Lymphocytes - metabolism Transcription Transcriptome - drug effects Transcriptome - genetics tRNA |
| title | Differential processing of small RNAs during endoplasmic reticulum stress |
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