Sequence analysis of mutations that affect the synthesis, assembly and enzymatic activity of the unc-54 myosin heavy chain of Caenorhabditis elegans

Dibb, Nick J.; Brown, D. M.; Karn, Jonathan; Moerman, Donald G.; Bolten, Suzanne L.; Waterston, Robert H.

doi:10.1016/0022-2836(85)90170-6

Cited by 128 publications

(71 citation statements)

References 27 publications

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“…www.rnajournal.org 2627 the natural stop, similar to what has been reported for other incompletely degraded PTC-containing transcripts (Dibb et al 1985;Bejsovec and Anderson 1988;Longman et al 2007). …”

Section: Prp-8(rr40) Causes Incomplete Cryptic Splicing Decreasing Isupporting

confidence: 76%

Suppressors of the cdc-25.1(gf)-associated intestinal hyperplasia reveal important maternal roles for prp-8 and a subset of splicing factors in C. elegans

Hebeisen

Drysdale²,

Roy³

2008

RNA

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The maternal contribution of gene products enables embryos to initiate their developmental program in the absence of zygotic gene expression. In Caenorhabditis elegans, maternal CDC-25.1 levels are tightly regulated to promote early cell divisions, while stabilization of this phosphatase by gain-of-function mutations gives rise to intestinal-specific hyperplasia. To identify regulators of CDC-25.1 levels and/or function, we performed a modifier screen of the cdc-25.1(gf)-dependent hyperplasia. One of the isolated suppressor mutants possesses a donor splice site mutation in prp-8, a key splicing factor of the U5-specific snRNP. prp-8(rr40) produces aberrant prp-8 splice variants that generate C-terminal truncations at the expense of wild-type prp-8. Levels of maternal transcripts are reduced, including cdc-25.1, while zygotic transcripts appear unperturbed, suggesting a germline-specific role for this splicing factor in regulating the splicing, and consequently, the steady-state levels of maternal transcripts. Using a novel feeding RNAi strategy we found that only a subset of splicing factors suppress cdc-25.1(gf), suggesting that they too may play specific roles in germ-line spliceosome function. In humans, mutations in the corresponding hPrp8 Cterminal domain result in retinitis pigmentosa, a retinal-specific disorder. Intriguingly, despite affecting the general splicing apparatus, both human and C. elegans show tissue-specific defects resulting from mutations in this key splicing component. Our findings suggest that in addition to its important regulatory function in the C. elegans germ line, prp-8(rr40) may provide further insight into the etiology of this splicing-associated human disorder.

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Section: Prp-8(rr40) Causes Incomplete Cryptic Splicing Decreasing Isupporting

confidence: 76%

Suppressors of the cdc-25.1(gf)-associated intestinal hyperplasia reveal important maternal roles for prp-8 and a subset of splicing factors in C. elegans

Hebeisen

Drysdale²,

Roy³

2008

RNA

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“…Analysis of the expression of the penultimate exon indicates that it is present in transcripts synthe sized in the adult thorax and absent in most other muscles (Bernstein et al 1986;Rozek and Davidson 1986), resulting in the muscle-specific localization of MHC isoforms with different carboxyl termini. We spec ulate that the carboxy-terminal sequence of MHC is critical to the assembly of myosin molecules into thick filaments (Kuczmarski and Spudich 1980;Dibb et al 1985) and that differences in the sequence of the carboxyl termini may result in myosin molecules with alternative as sembly properties. The tissue-specific expression of the other alternatively spliced exons within the MHC gene is poorly characterized.…”

Section: Muscle Diversity and The Generation Of Mhc Isoforms In Drosomentioning

confidence: 85%

“…In mutants Mhc^ and Mhc^^i where MHC transcripts accumulate to wildtype levels, the defects may be nonsense mutations within alternatively spliced exons that lead to the pro duction of normal levels of mRNA but result in the syn thesis of truncated MHC protein(s) within certain muscles. We (O'Dormell and Bernstein 1988) and others (Dibb et al 1985) have shown previously that many hy pomorphic MHC alleles code for MHC proteins that lack carboxy-terminal amino acids and fail to accimiulate as a result of their instability. Another possibility is that the Mhc^ and Mhc^^ alleles are missense mutations that result in the production of full-length unstable pro teins.…”

Section: Phenotypes Of the Homozygous-viable Mutants Suggest Defects mentioning

confidence: 99%

Ultrastructural and molecular analyses of homozygous-viable Drosophila melanogaster muscle mutants indicate there is a complex pattern of myosin heavy-chain isoform distribution.

O'Donnell¹,

Collier²,

Mogami³

et al. 1989

Genes Dev.

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We describe the ultrastructural and initial molecular characterization of four homozygous-viable, dominantflightless mutants of Drosophila melanogaster. Genetic mapping indicates that these mutations are inseparable from the known muscle myosin heavy-chain (MHC) allele Mhc^, and each mutation results in a muscle-specific reduction in MHC protein accumulation. The indirect flight muscles (IFMs) of each of these homozygous mutants fail to accumulate MHC, lack thick filaments, and do not display normal cylindrical myofibrils. As opposed to the null phenotype observed in the IFM, normal amounts of MHC accumulate in the leg muscles of three of these mutants, whereas the fourth mutant shows a 45% reduction in leg muscle MHC. The ultrastructure of the tergal depressor of the trochanter muscle (TDT, or jump muscle] is normal in one mutant, completely lacks thick filaments in a second mutant, and displays a reduction of thick filaments in two mutants. The thick filament reduction in this latter class of mutants is limited to the four smaller anterior cells of the TDT, indicating that the TDT is a mixed fiber-type muscle. Because all isoforms of muscle MHC are encoded by alternative splicing of transcripts from a single gene, our results suggest that there is a complex pattern of MHC isoform accumulation in Drosophila, The phenotypes of the homozygous-viable mutants provide evidence for the differential localization of MHC isoforms in different muscles, within the same muscle, and even within a single muscle cell. The mutant characteristics also suggest that the use of some alternative exons is shared among the IFM, TDT, and additional muscles whereas the use of others is unique to the IFM.[Key Words: Drosophila-, muscle mutants; myosin heavy chain; alternative RNA splicing]

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“…LGI: bli-3(e767), lin-17(n677), unc-11(e47), unc-73(e936), lin-44(n1792), unc-38(x20), dpy-5(e61), lin-35(n745), unc-13(e1091), lin-53(n833) (Ferguson and Horvitz 1989), and unc-54(e1092) (Dibb et al 1985). LGII: lin-31(n301), dpy-10(e128), tra-2(q276), rol-6(e187), dpl-1(n2994) (Ceol and Horvitz 2001;Thomas et al 2003), let-23(sy10, sy97), unc-4(e120), unc-53(n569), mex-1(it9), rol-1(e91), and lin-38(n751).…”

Section: Methodsunclassified

Identification and Classification of Genes That Act Antagonistically to let-60 Ras Signaling in Caenorhabditis elegans Vulval Development

Ceol¹,

Stegmeier²,

Harrison

et al. 2006

Genetics

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The synthetic multivulva (synMuv) genes negatively regulate Ras-mediated vulval induction in the nematode Caenorhabditis elegans. The synMuv genes define three classes, A, B, and C, such that double mutants carrying mutations in genes of any two classes are multivulva. The class B synMuv genes include lin-35, a homolog of the retinoblastoma (Rb) tumor suppressor gene, as well as homologs of genes that function with Rb in transcriptional regulation. We screened for additional synMuv mutations using a strategy different from that of previous synMuv genetic screens. Some of the mutations we recovered affect new synMuv genes. We present criteria for assigning synMuv mutations into different genetic classes. We also describe the molecular characterization of the class B synMuv gene lin-65.

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Sequence analysis of mutations that affect the synthesis, assembly and enzymatic activity of the unc-54 myosin heavy chain of Caenorhabditis elegans

Cited by 128 publications

References 27 publications

Suppressors of the cdc-25.1(gf)-associated intestinal hyperplasia reveal important maternal roles for prp-8 and a subset of splicing factors in C. elegans

Suppressors of the cdc-25.1(gf)-associated intestinal hyperplasia reveal important maternal roles for prp-8 and a subset of splicing factors in C. elegans

Ultrastructural and molecular analyses of homozygous-viable Drosophila melanogaster muscle mutants indicate there is a complex pattern of myosin heavy-chain isoform distribution.

Identification and Classification of Genes That Act Antagonistically to let-60 Ras Signaling in Caenorhabditis elegans Vulval Development

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