RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans
Messenger RNA translation is regulated by RNA-binding proteins and small non-coding RNAs called microRNAs. Even though we know the majority of RNA-binding proteins and microRNAs that regulate messenger RNA expression, evidence of interactions between the two remain elusive. The role of the RNA-bindi...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2013-01-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130151 |
| _version_ | 1819060614139478016 |
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| author | Alper Akay Ashley Craig Nicolas Lehrbach Mark Larance Ehsan Pourkarimi Jane E. Wright Angus Lamond Eric Miska Anton Gartner |
| author_facet | Alper Akay Ashley Craig Nicolas Lehrbach Mark Larance Ehsan Pourkarimi Jane E. Wright Angus Lamond Eric Miska Anton Gartner |
| author_sort | Alper Akay |
| collection | DOAJ |
| description | Messenger RNA translation is regulated by RNA-binding proteins and small non-coding RNAs called microRNAs. Even though we know the majority of RNA-binding proteins and microRNAs that regulate messenger RNA expression, evidence of interactions between the two remain elusive. The role of the RNA-binding protein GLD-1 as a translational repressor is well studied during Caenorhabditis elegans germline development and maintenance. Possible functions of GLD-1 during somatic development and the mechanism of how GLD-1 acts as a translational repressor are not known. Its human homologue, quaking (QKI), is essential for embryonic development. Here, we report that the RNA-binding protein GLD-1 in C. elegans affects multiple microRNA pathways and interacts with proteins required for microRNA function. Using genome-wide RNAi screening, we found that nhl-2 and vig-1, two known modulators of miRNA function, genetically interact with GLD-1. gld-1 mutations enhance multiple phenotypes conferred by mir-35 and let-7 family mutants during somatic development. We used stable isotope labelling with amino acids in cell culture to globally analyse the changes in the proteome conferred by let-7 and gld-1 during animal development. We identified the histone mRNA-binding protein CDL-1 to be, in part, responsible for the phenotypes observed in let-7 and gld-1 mutants. The link between GLD-1 and miRNA-mediated gene regulation is further supported by its biochemical interaction with ALG-1, CGH-1 and PAB-1, proteins implicated in miRNA regulation. Overall, we have uncovered genetic and biochemical interactions between GLD-1 and miRNA pathways. |
| first_indexed | 2024-12-21T14:29:47Z |
| format | Article |
| id | doaj.art-255f4e7074eb403999b2192121e81d59 |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-12-21T14:29:47Z |
| publishDate | 2013-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-255f4e7074eb403999b2192121e81d592022-12-21T19:00:31ZengThe Royal SocietyOpen Biology2046-24412013-01-0131110.1098/rsob.130151130151RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegansAlper AkayAshley CraigNicolas LehrbachMark LaranceEhsan PourkarimiJane E. WrightAngus LamondEric MiskaAnton GartnerMessenger RNA translation is regulated by RNA-binding proteins and small non-coding RNAs called microRNAs. Even though we know the majority of RNA-binding proteins and microRNAs that regulate messenger RNA expression, evidence of interactions between the two remain elusive. The role of the RNA-binding protein GLD-1 as a translational repressor is well studied during Caenorhabditis elegans germline development and maintenance. Possible functions of GLD-1 during somatic development and the mechanism of how GLD-1 acts as a translational repressor are not known. Its human homologue, quaking (QKI), is essential for embryonic development. Here, we report that the RNA-binding protein GLD-1 in C. elegans affects multiple microRNA pathways and interacts with proteins required for microRNA function. Using genome-wide RNAi screening, we found that nhl-2 and vig-1, two known modulators of miRNA function, genetically interact with GLD-1. gld-1 mutations enhance multiple phenotypes conferred by mir-35 and let-7 family mutants during somatic development. We used stable isotope labelling with amino acids in cell culture to globally analyse the changes in the proteome conferred by let-7 and gld-1 during animal development. We identified the histone mRNA-binding protein CDL-1 to be, in part, responsible for the phenotypes observed in let-7 and gld-1 mutants. The link between GLD-1 and miRNA-mediated gene regulation is further supported by its biochemical interaction with ALG-1, CGH-1 and PAB-1, proteins implicated in miRNA regulation. Overall, we have uncovered genetic and biochemical interactions between GLD-1 and miRNA pathways.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130151caenorhabditis elegansmirnagld-1let-7silac |
| spellingShingle | Alper Akay Ashley Craig Nicolas Lehrbach Mark Larance Ehsan Pourkarimi Jane E. Wright Angus Lamond Eric Miska Anton Gartner RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans Open Biology caenorhabditis elegans mirna gld-1 let-7 silac |
| title | RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans |
| title_full | RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans |
| title_fullStr | RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans |
| title_full_unstemmed | RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans |
| title_short | RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans |
| title_sort | rna binding protein gld 1 quaking genetically interacts with the mir 35 and the let 7 mirna pathways in caenorhabditis elegans |
| topic | caenorhabditis elegans mirna gld-1 let-7 silac |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130151 |
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