Large-scale RNAi screens identify novel genes that interact with the C. elegans retinoblastoma pathway as well as splicing-related components with synMuv B activity

Cerón, Julián; Rual, Jean François; Chandra, Abha; Dupuy, Denis; Vidal, Marc; Heuvel, Sander van den

doi:10.1186/1471-213x-7-30

Cited by 108 publications

(109 citation statements)

References 65 publications

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“…S3). Depletion of skr-10 or skr-17 did not lead to lethality in ubc-18 mutant animals, although these genes have been reported to have synthetic genetic interactions with lin-35 that result in larval lethality (21). We also did not observe genetic interactions with skr-8 or skr-9, which suppress the synthetic lethality of ubc-18; lin-35 animals (19).…”

Section: Genetic Interactions Between Ubc-18 and Genes Of The Scf E3mentioning

confidence: 54%

“…The candidate genes that we tested included five Cullins (cul-1, -2, -4, -5, -6) and SKP1-related (skr) and F-box genes chosen based on published genetic and physical interactions with members of the pharyngeal attachment pathway (18)(19)(20)(21). Consistent with previous reports (22), we found that only 25% of WT animals grown on cul-1(RNAi) survived to adulthood, which excluded cul-1(RNAi) from our primary screen.…”

Section: Genetic Interactions Between Ubc-18 and Genes Of The Scf E3mentioning

confidence: 99%

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Two functionally distinct E2/E3 pairs coordinate sequential ubiquitination of a common substrate in Caenorhabditis elegans development

Dove

Kemp

Bona

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Ubiquitination, the crucial posttranslational modification that regulates the eukaryotic proteome, is carried out by a trio of enzymes, known as E1 [ubiquitin (Ub)-activating enzyme], E2 (Ub-conjugating enzyme), and E3 (Ub ligase). Although most E2s can work with any of the three mechanistically distinct classes of E3s, the E2 UBCH7 is unable to function with really interesting new gene (RING)-type E3s, thereby restricting it to homologous to E6AP C-terminus (HECT) and RING-in-between-RING (RBR) E3s. The Caenorhabditis elegans UBCH7 homolog, UBC-18, plays a critical role in developmental processes through its cooperation with the RBR E3 ARI-1 (HHARI in humans). We discovered that another E2, ubc-3, interacts genetically with ubc-18 in an unbiased genome-wide RNAi screen in C. elegans. These two E2s have nonoverlapping biochemical activities, and each is dedicated to distinct classes of E3s. UBC-3 is the ortholog of CDC34 that functions specifically with Cullin-RING E3 ligases, such as SCF (Skp1-Cullin-F-box). Our genetic and biochemical studies show that UBCH7 (UBC-18) and the RBR E3 HHARI (ARI-1) coordinate with CDC34 (UBC-3) and an SCF E3 complex to ubiquitinate a common substrate, a SKP1-related protein. We show that UBCH7/HHARI primes the substrate with a single Ub in the presence of CUL-1, and that CDC34 is required to build chains onto the Ub-primed substrate. Our study reveals that the association and coordination of two distinct E2/E3 pairs play essential roles in a developmental pathway and suggests that cooperative action among E3s is a conserved feature from worms to humans.

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Section: Genetic Interactions Between Ubc-18 and Genes Of The Scf E3mentioning

confidence: 54%

Section: Genetic Interactions Between Ubc-18 and Genes Of The Scf E3mentioning

confidence: 99%

Two functionally distinct E2/E3 pairs coordinate sequential ubiquitination of a common substrate in Caenorhabditis elegans development

Dove

Kemp

Bona

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…1,5 Several genome-wide small interfering RNA (siRNA) screens designed to identify genes with roles in genome maintenance and cell cycle progression have reported a role for spliceosome components in these processes. [6][7][8][9][10][11][12] Mutations in multiple spliceosome subunits have been found in leukemia, myeloid neoplasms, and some solid tumors, 13,14 suggesting that spliceosome defects might promote tumorigenesis perhaps through its roles in genome maintenance and cell division.…”

Section: Introductionmentioning

confidence: 99%

Graded requirement for the spliceosome in cell cycle progression

Karamysheva¹,

Díaz-Martínez

Warrington

et al. 2015

Cell Cycle

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Genome stability is ensured by multiple surveillance mechanisms that monitor the duplication, segregation, and integrity of the genome throughout the cell cycle. Depletion of components of the spliceosome, a macromolecular machine essential for mRNA maturation and gene expression, has been associated with increased DNA damage and cell cycle defects. However, the specific role for the spliceosome in these processes has remained elusive, as different cell cycle defects have been reported depending on the specific spliceosome subunit depleted. Through a detailed cell cycle analysis after spliceosome depletion, we demonstrate that the spliceosome is required for progression through multiple phases of the cell cycle. Strikingly, the specific cell cycle phenotype observed after spliceosome depletion correlates with the extent of depletion. Partial depletion of a core spliceosome component results in defects at later stages of the cell cycle (G2 and mitosis), whereas a more complete depletion of the same component elicits an early cell cycle arrest in G1. We propose a quantitative model in which different functional dosages of the spliceosome are required for different cell cycle transitions.

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“…Large-scale surveys have also been done by injecting in vitro transcribed dsRNAs [20,22] or soaking animals in dsRNA solution [33]. However, as it is technically simpler to deliver dsRNA by feeding, efforts were made to generate libraries of bacterial 'feeding' plasmids that represent each predicted gene [21] or a substantial portion of expressed genes [34]. Many researchers have chosen to use the commercially available library generated by the Ahringer laboratory [21,32].…”

Section: Analysis Of Specific Developmental Processes and Biochemicalmentioning

confidence: 99%

Studying gene function in Caenorhabditis elegans using RNA-mediated interference

Maine¹

2008

Briefings in Functional Genomics and Proteomics

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The RNA interference (RNAi) method for targeted gene silencing is widely used in Caenorhabditis elegans for largescale functional genomic studies, analysis of limited gene sets and detailed analysis of individual gene function. The application of RNAi has identified genes that participate in various aspects of development, physiology and cell biology. In addition, RNAi has been used to identify interacting genes and to study functionally redundant genes. This review discusses the various applications of RNAi in C. elegans, focusing particularly on the analysis of developmental processes.

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Large-scale RNAi screens identify novel genes that interact with the C. elegans retinoblastoma pathway as well as splicing-related components with synMuv B activity

Cited by 108 publications

References 65 publications

Two functionally distinct E2/E3 pairs coordinate sequential ubiquitination of a common substrate in Caenorhabditis elegans development

Two functionally distinct E2/E3 pairs coordinate sequential ubiquitination of a common substrate in Caenorhabditis elegans development

Graded requirement for the spliceosome in cell cycle progression

Studying gene function in Caenorhabditis elegans using RNA-mediated interference

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