microRNA-mediated translation repression through GYF-1 and IFE-4 in C. elegans development
| Autor: | Nahum Sonenberg, Mathieu N. Flamand, James A. Wohlschlegel, Alice M Lambert, Vinay K. Mayya, Thomas F. Duchaine, Seyed Mehdi Jafarnejad |
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| Rok vydání: | 2021 |
| Předmět: |
Proteomics
AcademicSubjects/SCI00010 NAR Breakthrough Article Repressor Biology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Protein Domains microRNA Genetics medicine Animals RNA-Induced Silencing Complex Gene silencing Gene Silencing Caenorhabditis elegans Caenorhabditis elegans Proteins Psychological repression 030304 developmental biology 0303 health sciences Mutation Effector Gene Expression Regulation Developmental Translation (biology) biology.organism_classification Cell biology MicroRNAs Eukaryotic Initiation Factor-4E Protein Biosynthesis Genes Lethal 030217 neurology & neurosurgery |
| Zdroj: | Mayya, V K, Flamand, M N, Lambert, A M, Jafarnejad, S M, Wohlschlegel, J A, Sonenberg, N & Duchaine, T F 2021, ' microRNA-mediated translation repression through GYF-1 and IFE-4 in C. elegans development ', Nucleic Acids Research . https://doi.org/10.1093/nar/gkab162 Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkab162 |
| Popis: | microRNA (miRNA)-mediated gene silencing is enacted through the recruitment of effector proteins that direct translational repression or degradation of mRNA targets, but the relative importance of their activities for animal development remains unknown. Our concerted proteomic surveys identified the uncharacterized GYF-domain encoding protein GYF-1 and its direct interaction with IFE-4, the ortholog of the mammalian translation repressor 4EHP, as key miRNA effector proteins in Caenorhabditis elegans. Recruitment of GYF-1 protein to mRNA reporters in vitro or in vivo leads to potent translation repression without affecting the poly(A) tail or impinging on mRNA stability. Loss of gyf-1 is synthetic lethal with hypomorphic alleles of embryonic miR-35–42 and larval (L4) let-7 miRNAs, which is phenocopied through engineered mutations in gyf-1 that abolish interaction with IFE-4. GYF-1/4EHP function is cascade-specific, as loss of gyf-1 had no noticeable impact on the functions of other miRNAs, including lin-4 and lsy-6. Overall, our findings reveal the first direct effector of miRNA-mediated translational repression in C. elegans and its physiological importance for the function of several, but likely not all miRNAs. |
| Databáze: | OpenAIRE |
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