Abstract：
:Selection of suppressor mutations that correct growth defects caused by substitutions in an RNA or protein can reveal functionally important molecular structures and interactions in living cells. This approach is particularly useful for the study of complex biological pathways involving many macromolecules, such as premessenger RNA (pre-mRNA) splicing. When a sufficiently large number of suppressor mutations is obtained and structural information is available, it is possible to generate detailed models of molecular function. However, the laborious and expensive task of identifying suppressor mutations in whole-genome selections limits the utility of this approach. Here I show that a custom targeted sequencing panel can greatly accelerate the identification of suppressor mutations in the Saccharomyces cerevisiae genome. Using a panel that targets 112 genes encoding pre-mRNA splicing factors, I identified 27 unique mutations in six protein-coding genes that each overcome the cold-sensitive block to spliceosome activation caused by a substitution in U4 small nuclear RNA. When mapped to existing structures of spliceosomal complexes, the identified suppressors implicate specific molecular contacts between the proteins Brr2, Prp6, Prp8, Prp31, Sad1, and Snu114 as functionally important in an early step of catalytic activation of the spliceosome. This approach shows great promise for elucidating the allosteric cascade of molecular interactions that direct accurate and efficient pre-mRNA splicing and should be broadly useful for understanding the dynamics of other complex biological assemblies or pathways.
journal_name
Geneticsjournal_title
Geneticsauthors
Brow DAdoi
10.1534/genetics.119.301922subject
Has Abstractpub_date
2019-05-01 00:00:00pages
111-124issue
1eissn
0016-6731issn
1943-2631pii
genetics.119.301922journal_volume
212pub_type
杂志文章相关文献
GENETICS文献大全abstract：:The parasitoid wasp Nasonia vitripennis is an emerging model organism for developmental and behavioral genetics. It reproduces by haplodiploidy; males typically develop parthenogenetically from haploid eggs and females from fertilized diploid eggs. A polyploid mutant strain is available in which females are triploid a...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.105.044743
更新日期：2006-02-01 00:00:00
abstract：:The correct wiring of neuronal circuits depends on outgrowth and guidance of neuronal processes during development. In the past two decades, great progress has been made in understanding the molecular basis of axon outgrowth and guidance. Genetic analysis in Caenorhabditis elegans has played a key role in elucidating ...
journal_title：Genetics
pub_type： 杂志文章,评审
doi：10.1534/genetics.115.186262
更新日期：2016-11-01 00:00:00
abstract：:The ability of autonomously replicating plasmids to recombine in mammalian cells was investigated. Two deletion plasmids of the eukaryotic-prokaryotic shuttle vector pSV2neo were cotransfected into transformed monkey COS cells. Examination of the low molecular weight DNA isolated after 48 hr of incubation revealed tha...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1985-10-01 00:00:00
abstract：:Understanding how variation in reproductive success is related to demography is a critical component in understanding the life history of an organism. Parentage analysis using molecular markers can be used to estimate the reproductive success of different groups of individuals in natural populations. Previous models h...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.106.067066
更新日期：2007-08-01 00:00:00
abstract：:Mutagenic DNA repair (MDR) employs low-fidelity DNA polymerases capable of replicating past DNA lesions resulting from exposure to high-energy ultraviolet radiation (UVR). MDR confers UVR tolerance and activation initiates a transient mutator phenotype that may provide opportunities for adaptation. To investigate the ...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.108.096131
更新日期：2009-01-01 00:00:00
abstract：:Gene expression in Anopheles gambiae shows a deficiency of testis-expressed genes on the X chromosome associated with an excessive movement of retrogene duplication. We suggest that the degeneration of sex chromosomes in this monandrous species is likely the result of pressures from X inactivation, dosage compensation...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.111.133157
更新日期：2011-11-01 00:00:00
abstract：:We have examined the stability of the tandemly repeated genes that encode the ribosomal RNA in Coprinus cinereus. These genes are contained within two linked HindIII fragments in a 3.0-Mb chromosome. We monitored the size of these fragments in both mitotic and meiotic segregants using the contour-clamped homogeneous e...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:Selection during evolution, whether natural or artificial, acts through the phenotype. For multifaceted phenotypes such as plant and inflorescence architecture, the underlying genetic architecture is comprised of a complex network of interacting genes rather than single genes that act independently to determine the tr...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.117.300071
更新日期：2017-10-01 00:00:00
abstract：:Mutants arising spontaneously from sporulated cultures of certain strains of yeast, Saccharomyces cerevisiae, contained deletions of the CYC1 gene which controls the primary structure of iso-1-cytochrome c. At least 60 different kinds of deletions were uncovered among the 104 deletions examined and these ranged in len...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1975-09-01 00:00:00
abstract：:Efficient haplotyping in pedigrees is important for the fine mapping of quantitative trait locus (QTL) or complex disease genes. To reconstruct haplotypes efficiently for a large pedigree with a large number of linked loci, two algorithms based on conditional probabilities and likelihood computations are presented. Th...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.103.021055
更新日期：2004-08-01 00:00:00
abstract：:In female mammalian cells, the inactive X chromosome is replicated late in S phase while the active X chromosome is replicated earlier. The replication times of the X chromosomes reflect a general trend in which late replication is associated with gene repression and earlier replication with transcriptional competence...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.105.043026
更新日期：2005-10-01 00:00:00
abstract：:How many genes contribute to reproductive isolation between closely related species? We determined the number of genes located in the 9D-12B region of the Drosophila mauritiana X chromosome that cause hybrid male sterility in a D. simulans background. Previous low resolution studies suggested that a single hybrid ster...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:Populations of several co-existing species of Simocephalus were examined electrophoretically at 11 enzyme loci. The prevailing pattern was one of extensive allelic substitution between species and low levels of polymorphism (0-10%) within species. Genetic identity values between species were very low (10-50%). These r...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
abstract：:Additional experiments with homologous as well as heterologous hybridization confirmed our previous finding in Sciara coprophila that XX females have nearly twice the number of ribosomal RNA cistrons as XO males. A comparison between two different X' chromosomes revealed that only the one carrying the irradiation-indu...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
abstract：:We showed that sufficient overexpression of the wild-type recF gene interfered with three normal cell functions: (1) UV induction of transcription from the LexA-protein-repressed sulA promoter, (2) UV resistance and (3) cell viability at 42 degrees. To show this, we altered a low-level overexpressing recF+ plasmid wit...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:The Mre11/Rad50/Nbs1 (MRN) complex is required for eukaryotic DNA double-strand break (DSB) repair and meiotic recombination. We cloned the Coprinus cinereus rad50 gene and showed that it corresponds to the complementation group previously named rad12, identified mutations in 15 rad50 alleles, and mapped two of the mu...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.108.092775
更新日期：2008-12-01 00:00:00
abstract：:The Polymerase Associated Factor 1 complex (Paf1C) is a multifunctional regulator of eukaryotic gene expression important for the coordination of transcription with chromatin modification and post-transcriptional processes. In this study, we investigated the extent to which the functions of Paf1C combine to regulate t...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.119.302262
更新日期：2019-07-01 00:00:00
abstract：:Mathematical models are presented for the evolution of postmating and premating reproductive isolation. In the case of postmating isolation it is assumed that hybrid sterility or inviability is caused by incompatibility of alleles at one or two loci, and evolution of reproductive isolation occurs by random fixation of...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:The Saccharomyces cerevisiae nuclear membrane is part of a complex nuclear envelope environment also containing chromatin, integral and peripheral membrane proteins, and large structures such as nuclear pore complexes (NPCs) and the spindle pole body. To study how properties of the nuclear membrane affect nuclear enve...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.110.119149
更新日期：2010-11-01 00:00:00
abstract：:In yeast meiotic recombination, alleles used as genetic markers fall into two classes as regards their fate when incorporated into heteroduplex DNA. Normal alleles are those that form heteroduplexes that are nearly always recognized and corrected by the mismatch repair system operating in meiosis. High PMS (postmeioti...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
abstract：:Trichome development in Arabidopsis thaliana is a well-characterized model for the study of plant cell differentiation. Two genes that play an essential role in the initiation of trichome development are GL1 and TTG. Mutations in either gene prevent the initiation of most trichomes. The GL1 gene encodes a myb-related ...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1999-04-01 00:00:00
abstract：:Conversion between duplicated genes limits their independent evolution. Models in which conversion frequencies decrease as genes diverge are examined to determine conditions under which genes can "escape" further conversion and hence escape from a gene family. A review of results from various recombination systems sug...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1987-11-01 00:00:00
abstract：:Maize (Zea mays L.) serves as model plant for heterosis research and is the crop where hybrid breeding was pioneered. We analyzed genomic and phenotypic data of 1254 hybrids of a typical maize hybrid breeding program based on the important Dent × Flint heterotic pattern. Our main objectives were to investigate genome ...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.114.165860
更新日期：2014-08-01 00:00:00
abstract：:The first five steps in de novo purine biosynthesis are involved in the formation of the 4-amino-5-hydroxymethyl-2-methyl pyrimidine (HMP) moiety of thiamine. We show here that the first enzyme in de novo purine biosynthesis, PurF, is required for thiamine synthesis during aerobic growth on some but not other carbon s...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:The fine-scale pattern of correlated paternity was characterized within a population of the narrow-endemic model plant species, Centaurea corymbosa, using microsatellites and natural progeny arrays. We used classical approaches to assess correlated mating within sibships and developed a new method based on pairwise ki...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.104.027714
更新日期：2004-11-01 00:00:00
abstract：:Genetic adaptation to external stimuli occurs through the combined action of mutation and selection. A central problem in genetics is to identify loci responsive to specific selective constraints. Many tests have been proposed to identify the genomic signatures of natural selection by quantifying the skew in the site ...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.113.152587
更新日期：2013-09-01 00:00:00
abstract：:DNA topoisomerases, enzymes that alter the superhelicity of DNA, have been implicated in such critical cellular functions as transcription, DNA replication, and recombination. In the yeast Saccharomyces cerevisiae, a null mutation in the gene encoding topoisomerase I (TOP1) causes elevated levels of mitotic recombinat...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:Peroxisomes are organelles containing a diverse array of enzymes. In fungi they are important for carbon source utilization, pathogenesis, development, and secondary metabolism. We have studied Aspergillus nidulans peroxin (pex) mutants isolated by virtue of their inability to grow on butyrate or by the inactivation o...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.107.085795
更新日期：2008-03-01 00:00:00
abstract：:We describe allelic variation at 28 gene loci in natural populations of D. willistoni. Seventy samples were studied from localities extending from Mexico and Florida, through Central America, the West Indies, and tropical South America, down to South Brazil. At least several hundred, and often several thousand, genome...
journal_title：Genetics
pub_type： 杂志文章
doi：
更新日期：1972-01-01 00:00:00
abstract：:Adherence, an important virulence factor, is mediated by the EPA (Epithelial Adhesin) genes in the opportunistic pathogen Candida glabrata Expression of adhesin-encoding genes requires tight regulation to respond to harsh environmental conditions within the host. The majority of EPA genes are localized in subtelomeric...
journal_title：Genetics
pub_type： 杂志文章
doi：10.1534/genetics.118.301202
更新日期：2018-09-01 00:00:00
