A universal strategy for regulating mRNA translation in prokaryotic and eukaryotic cells
We describe a simple strategy to control mRNA translation in both prokaryotic and eukaryotic cells which relies on a unique protein-RNA interaction. Specifically, we used the Pumilio/FBF (PUF) protein to repress translation by binding in between the ribosome binding site (RBS) and the start codon (i...
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Veröffentlicht in: | Nucleic acids research 2015-04, Vol.43 (8), p.4353-4362 |
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creator | Cao, Jicong Arha, Manish Sudrik, Chaitanya Mukherjee, Abhirup Wu, Xia Kane, Ravi S |
description | We describe a simple strategy to control mRNA translation in both prokaryotic and eukaryotic cells which relies on a unique protein-RNA interaction. Specifically, we used the Pumilio/FBF (PUF) protein to repress translation by binding in between the ribosome binding site (RBS) and the start codon (in Escherichia coli), or by binding to the 5' untranslated region of target mRNAs (in mammalian cells). The design principle is straightforward, the extent of translational repression can be tuned and the regulator is genetically encoded, enabling the construction of artificial signal cascades. We demonstrate that this approach can also be used to regulate polycistronic mRNAs; such regulation has rarely been achieved in previous reports. Since the regulator used in this study is a modular RNA-binding protein, which can be engineered to target different 8-nucleotide RNA sequences, our strategy could be used in the future to target endogenous mRNAs for regulating metabolic flows and signaling pathways in both prokaryotic and eukaryotic cells. |
doi_str_mv | 10.1093/nar/gkv290 |
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Specifically, we used the Pumilio/FBF (PUF) protein to repress translation by binding in between the ribosome binding site (RBS) and the start codon (in Escherichia coli), or by binding to the 5' untranslated region of target mRNAs (in mammalian cells). The design principle is straightforward, the extent of translational repression can be tuned and the regulator is genetically encoded, enabling the construction of artificial signal cascades. We demonstrate that this approach can also be used to regulate polycistronic mRNAs; such regulation has rarely been achieved in previous reports. 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Since the regulator used in this study is a modular RNA-binding protein, which can be engineered to target different 8-nucleotide RNA sequences, our strategy could be used in the future to target endogenous mRNAs for regulating metabolic flows and signaling pathways in both prokaryotic and eukaryotic cells.</description><subject>5' Untranslated Regions</subject><subject>Binding Sites</subject><subject>Cell Engineering</subject><subject>Escherichia coli</subject><subject>Escherichia coli - genetics</subject><subject>Gene Expression Regulation</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Protein Biosynthesis</subject><subject>Protein Structure, Tertiary</subject><subject>Response Elements</subject><subject>Ribosomes - metabolism</subject><subject>Synthetic Biology and Bioengineering</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1LAzEQhoMoWj8u_gDJUYS1ySZpkotQil8gCqLgLaTZ2XXtNqnJbqH_3i3VoidPw8w8vLwzL0KnlFxSotnQ2zisZstckx00oGyUZ1yP8l00IIyIjBKuDtBhSh-EUE4F30cHuVBcCKUH6G2MO18vISbb4NRG20K1wmWIOELVNbatfYXnz49j3O98Wg-Cx7XHixhmNq5CWztsfYGh27YOmiYdo73SNglOvusRer25fpncZQ9Pt_eT8UPmuJRt5nLttCYlI5CDogDCKRCSKSH0lFhRFLKYlqB1oUvtlC651o5yqYR1BWMlO0JXG91FN51D4cD3RhuziPW892OCrc3fja_fTRWWhnMqqeK9wPm3QAyfHaTWzOu0PsF6CF0yVPZv0zTno__RkVSSK5WrHr3YoC6GlCKUW0eUmHVqpk_NbFLr4bPfN2zRn5jYFzvDloc</recordid><startdate>20150430</startdate><enddate>20150430</enddate><creator>Cao, Jicong</creator><creator>Arha, Manish</creator><creator>Sudrik, Chaitanya</creator><creator>Mukherjee, Abhirup</creator><creator>Wu, Xia</creator><creator>Kane, Ravi S</creator><general>Oxford University Press</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>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20150430</creationdate><title>A universal strategy for regulating mRNA translation in prokaryotic and eukaryotic cells</title><author>Cao, Jicong ; Arha, Manish ; Sudrik, Chaitanya ; Mukherjee, Abhirup ; Wu, Xia ; Kane, Ravi S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-c29c990f30e2e81ee5c8e5738559b0a5dd7dbfe99d9f9c89f499c14785acd33f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>5' Untranslated Regions</topic><topic>Binding Sites</topic><topic>Cell Engineering</topic><topic>Escherichia coli</topic><topic>Escherichia coli - genetics</topic><topic>Gene Expression Regulation</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Protein Biosynthesis</topic><topic>Protein Structure, Tertiary</topic><topic>Response Elements</topic><topic>Ribosomes - metabolism</topic><topic>Synthetic Biology and Bioengineering</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cao, Jicong</creatorcontrib><creatorcontrib>Arha, Manish</creatorcontrib><creatorcontrib>Sudrik, Chaitanya</creatorcontrib><creatorcontrib>Mukherjee, Abhirup</creatorcontrib><creatorcontrib>Wu, Xia</creatorcontrib><creatorcontrib>Kane, Ravi S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cao, Jicong</au><au>Arha, Manish</au><au>Sudrik, Chaitanya</au><au>Mukherjee, Abhirup</au><au>Wu, Xia</au><au>Kane, Ravi S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A universal strategy for regulating mRNA translation in prokaryotic and eukaryotic cells</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2015-04-30</date><risdate>2015</risdate><volume>43</volume><issue>8</issue><spage>4353</spage><epage>4362</epage><pages>4353-4362</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>We describe a simple strategy to control mRNA translation in both prokaryotic and eukaryotic cells which relies on a unique protein-RNA interaction. 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subjects | 5' Untranslated Regions Binding Sites Cell Engineering Escherichia coli Escherichia coli - genetics Gene Expression Regulation HEK293 Cells Humans Protein Biosynthesis Protein Structure, Tertiary Response Elements Ribosomes - metabolism Synthetic Biology and Bioengineering |
title | A universal strategy for regulating mRNA translation in prokaryotic and eukaryotic cells |
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