Faculty Opinions recommendation of The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel.

Two genomic sequences that share homology with Rp11215, the gene encoding the largest subunit of RNA polymerase II in Drosophila melanogaster, have been isolated from the nematode Caenorhabditis elegans. One of these sequences was physically mapped on chromosome IV within a region deleted by the deficiency mDf4, 25 kilobases (kb) from the left deficiency breakpoint. This position corresponds to ama-1 (resistance to alpha-amanitin), a gene shown previously to encode a subunit of RNA polymerase II. Northern (RNA) blotting and DNA sequencing revealed that ama-1 spans 10 kb, is punctuated by 11 introns, and encodes a 5.9-kb mRNA. A cDNA clone was isolated and partially sequenced to confirm the 3' end and several splice junctions. Analysis of the inferred 1,859-residue ama-1 product showed considerable identity with the largest subunit of RNAP II from other organisms, including the presence of a zinc finger motif near the amino terminus, and a carboxyl-terminal domain of 42 tandemly reiterated heptamers with the consensus Tyr Ser Pro Thr Ser Pro Ser. The latter domain was found to be encoded by four exons. In addition, the sequence oriented ama-1 transcription with respect to the genetic map. The second C. elegans sequence detected with the Drosophila probe, named rpc-1, was found to encode a 4.8-kb transcript and hybridized strongly to the gene encoding the largest subunit of RNA polymerase III from yeast, implicating rpc-1 as encoding the analogous peptide in the nematode. By contrast with ama-1, rpc-1 was not deleted by mDf4 or larger deficiencies examined, indicating that these genes are no closer than 150 kb. Genes flanking ama-1, including two collagen genes, also have been identified.

Download Full-text

C. elegans homologue of the Caf1 gene, which encodes a subunit of the CCR4-NOT complex, is essential for embryonic and larval development and for meiotic progression

Gene ◽

10.1016/j.gene.2005.05.023 ◽

2005 ◽

Vol 358 ◽

pp. 73-81 ◽

Cited By ~ 30

Author(s):

Laurent Molin ◽

Alain Puisieux

Keyword(s):

Larval Development ◽

C Elegans ◽

Meiotic Progression ◽

A Subunit ◽

Embryonic And Larval Development

Download Full-text

A cyclin-dependent kinase, CDK11/p58, represses cap-dependent translation during mitosis

Cellular and Molecular Life Sciences ◽

10.1007/s00018-019-03436-3 ◽

2020 ◽

Vol 77 (22) ◽

pp. 4693-4708 ◽

Cited By ~ 1

Author(s):

Sihyeon An ◽

Oh Sung Kwon ◽

Jinbae Yu ◽

Sung Key Jang

Keyword(s):

Translational Regulation ◽

Ectopic Expression ◽

Translational Repression ◽

Serine Threonine Kinase ◽

Threonine Kinase ◽

C Elegans ◽

Target Sites ◽

M Phase ◽

A Subunit ◽

Cycle Dependent

Abstract During mitosis, translation of most mRNAs is strongly repressed; none of the several explanatory hypotheses suggested can fully explain the molecular basis of this phenomenon. Here we report that cyclin-dependent CDK11/p58—a serine/threonine kinase abundantly expressed during M phase—represses overall translation by phosphorylating a subunit (eIF3F) of the translation factor eIF3 complex that is essential for translation initiation of most mRNAs. Ectopic expression of CDK11/p58 strongly repressed cap-dependent translation, and knockdown of CDK11/p58 nullified the translational repression during M phase. We identified the phosphorylation sites in eIF3F responsible for M phase-specific translational repression by CDK11/p58. Alanine substitutions of CDK11/p58 target sites in eIF3F nullified its effects on cell cycle-dependent translational regulation. The mechanism of translational regulation by the M phase-specific kinase, CDK11/p58, has deep evolutionary roots considering the conservation of CDK11 and its target sites on eIF3F from C. elegans to humans.

Download Full-text

Alternative polyadenylation is a determinant of oncogenic Ras function

10.1101/2020.06.08.140145 ◽

2020 ◽

Author(s):

Aishwarya Subramanian ◽

Mathew Hall ◽

Huayun Hou ◽

Marat Mufteev ◽

Bin Yu ◽

...

Keyword(s):

Epithelial To Mesenchymal Transition ◽

Alternative Polyadenylation ◽

Untranslated Regions ◽

Multidrug Transporter ◽

Mesenchymal Transition ◽

C Elegans ◽

Activating Mutations ◽

Oncogenic Ras ◽

A Subunit ◽

P21 Activated Kinase

ABSTRACTAlternative polyadenylation of pre-mRNA has been recently shown to play important roles in development and cancer. Activating mutations in the Ras oncogene are common drivers of many human cancers but the mechanisms by which they cooperate with alternative polyadenylation are not known. By exploiting the genetics of C. elegans, we identified cfim-1/CFIm25, a subunit of the alternative polyadenylation machine, as a key determinant of hyperactive Ras function. Ablation of cfim-1 increased penetrance of multivulva phenotype in let-60/Ras gain-of-function (gf) mutant through shortening of transcripts at the 3’ untranslated region, including p21 activated kinase pak-1/PAK1 and multidrug transporter mrp-5/ABCC1. Depletion of CFIm25 in human KRAS-driven cancer cells resulted in a similar shortening of 3’ untranslated regions in the PAK1 and ABCC1 transcripts, which caused an epithelial-to-mesenchymal transition and increased cell migration. Exploiting the mechanisms by which alternative polyadenylation affects activated oncogene output could offer novel approaches for the treatment of Ras-driven tumors.

Download Full-text

Impaired chromosome segregation results in sperms with excess centrosomes in emb-27APC6 mutant C. elegans

10.1101/449538 ◽

2018 ◽

Cited By ~ 1

Author(s):

Tomo Kondo ◽

Akatsuki Kimura

Keyword(s):

Cell Division ◽

Chromosome Segregation ◽

Anaphase Promoting Complex ◽

C Elegans ◽

Secondary Spermatocyte ◽

Centrosome Separation ◽

A Subunit ◽

Excess Number

AbstractThe anaphase-promoting complex (APC) is a major regulator of chromosome segregation and is implicated in centriole engagement, whose de-regulation causes abnormal number of centrosomes. The emb-27 gene in C. elegans encodes a subunit of APC. The paternal emb-27 mutant was reported to show cell division with multiple furrows, suggesting the presence of excess centrosomes. In this study, we examined the number of centrosomes and the mechanism underlying de-regulation of centrosome number in emb-27 mutants. Our observations indicated excess centrosomes in emb-27 sperms, which resulted in zygotes with excess centrosomes. Further, the secondary spermatocyte of emb-27 produced reduced number of spermatids, which is likely the direct cause of the excess number of centrosomes per sperm. We propose that a chromosome segregation defect in emb-27 induced centrosome separation defect, resulting in reduced number of buds. Additionally, treatment with cytoskeletal inhibiting drugs indicated presence of three kinds of forces working in combination to move the centrosomes into the spermatids. The present study suggested a novel role of microtubule in the budding cytokinesis of spermatocytes.

Download Full-text

KNL1 and the CENP-H/I/K Complex Coordinately Direct Kinetochore Assembly in Vertebrates

Molecular Biology of the Cell ◽

10.1091/mbc.e07-10-1051 ◽

2008 ◽

Vol 19 (2) ◽

pp. 587-594 ◽

Cited By ~ 116

Author(s):

Iain M. Cheeseman ◽

Tetsuya Hori ◽

Tatsuo Fukagawa ◽

Arshad Desai

Keyword(s):

Cell Division ◽

Caenorhabditis Elegans ◽

Chromosome Segregation ◽

Centromeric Chromatin ◽

C Elegans ◽

Kinetochore Assembly ◽

Assembly Mechanism ◽

Ndc80 Complex ◽

A Subunit ◽

Assembly Pathways

Chromosome segregation during mitosis requires the assembly of a large proteinaceous structure termed the kinetochore. In Caenorhabditis elegans, KNL-1 is required to target multiple outer kinetochore proteins. Here, we demonstrate that the vertebrate KNL1 counterpart is essential for chromosome segregation and is required to localize a subset of outer kinetochore proteins. However, unlike in C. elegans, depletion of vertebrate KNL1 does not abolish kinetochore localization of the microtubule-binding Ndc80 complex. Instead, we show that KNL1 and CENP-K, a subunit of a constitutively centromere-associated complex that is missing from C. elegans, coordinately direct Ndc80 complex localization. Simultaneously reducing both hKNL1 and CENP-K function abolishes all aspects of kinetochore assembly downstream of centromeric chromatin and causes catastrophic chromosome segregation defects. These findings explain discrepancies in kinetochore assembly pathways between different organisms and reveal a surprising plasticity in the assembly mechanism of an essential cell division organelle.

Download Full-text

unc-8, a DEG/ENaC Family Member, Encodes a Subunit of a Candidate Mechanically Gated Channel That Modulates C. elegans Locomotion

Neuron ◽

10.1016/s0896-6273(01)80050-7 ◽

1997 ◽

Vol 18 (1) ◽

pp. 107-119 ◽

Cited By ~ 137

Author(s):

Nektarios Tavernarakis ◽

Wayne Shreffler ◽

Shiliang Wang ◽

Monica Driscoll

Keyword(s):

Family Member ◽

C Elegans ◽

Gated Channel ◽

A Subunit

Download Full-text

Molecular cloning and sequencing of ama-1, the gene encoding the largest subunit of Caenorhabditis elegans RNA polymerase II.

Molecular and Cellular Biology ◽

10.1128/mcb.9.10.4119 ◽

1989 ◽

Vol 9 (10) ◽

pp. 4119-4130 ◽

Cited By ~ 50

Author(s):

D M Bird ◽

D L Riddle

Keyword(s):

Caenorhabditis Elegans ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Rna Polymerase Iii ◽

Gene Encoding ◽

C Elegans ◽

A Subunit ◽

Rnap Ii ◽

Collagen Genes ◽

Splice Junctions

Two genomic sequences that share homology with Rp11215, the gene encoding the largest subunit of RNA polymerase II in Drosophila melanogaster, have been isolated from the nematode Caenorhabditis elegans. One of these sequences was physically mapped on chromosome IV within a region deleted by the deficiency mDf4, 25 kilobases (kb) from the left deficiency breakpoint. This position corresponds to ama-1 (resistance to alpha-amanitin), a gene shown previously to encode a subunit of RNA polymerase II. Northern (RNA) blotting and DNA sequencing revealed that ama-1 spans 10 kb, is punctuated by 11 introns, and encodes a 5.9-kb mRNA. A cDNA clone was isolated and partially sequenced to confirm the 3' end and several splice junctions. Analysis of the inferred 1,859-residue ama-1 product showed considerable identity with the largest subunit of RNAP II from other organisms, including the presence of a zinc finger motif near the amino terminus, and a carboxyl-terminal domain of 42 tandemly reiterated heptamers with the consensus Tyr Ser Pro Thr Ser Pro Ser. The latter domain was found to be encoded by four exons. In addition, the sequence oriented ama-1 transcription with respect to the genetic map. The second C. elegans sequence detected with the Drosophila probe, named rpc-1, was found to encode a 4.8-kb transcript and hybridized strongly to the gene encoding the largest subunit of RNA polymerase III from yeast, implicating rpc-1 as encoding the analogous peptide in the nematode. By contrast with ama-1, rpc-1 was not deleted by mDf4 or larger deficiencies examined, indicating that these genes are no closer than 150 kb. Genes flanking ama-1, including two collagen genes, also have been identified.

Download Full-text

The glycomes of Caenorhabditis elegans and other model organisms

Biochemical Society Symposium ◽

10.1042/bss0690117 ◽

2002 ◽

Vol 69 ◽

pp. 117-134 ◽

Cited By ~ 47

Author(s):

Stuart M. Haslam ◽

David Gems ◽

Howard R. Morris ◽

Anne Dell

Keyword(s):

Caenorhabditis Elegans ◽

Current Knowledge ◽

Structural Data ◽

Model Organisms ◽

Entire Genome ◽

C Elegans ◽

The Face ◽

Area Of Concern ◽

Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

Download Full-text