kep1
 interacts genetically with
 dredd
 /
 Caspase-8
 , and
 kep1
 mutants alter the balance of
 dredd
 isoforms

Fruscio, Marco Di; Styhler, Sylvia; Wikholm, Eva; Boulanger, Marie-Chloé; Lasko, Paul; Richard, Stéphane

doi:10.1073/pnas.0236048100

Cited by 21 publications

(18 citation statements)

References 51 publications

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“…Considering that D. melanogaster kep1 is a splicing factor responsible for the alternative splicing of the Drosophila caspase molecule dredd [16], the observation above led us to speculate that new kep1 family genes might regulate the pre-mRNA processing of genes required for spermatogenesis and sperm function.…”

Section: Resultsmentioning

confidence: 99%

A Young Drosophila Duplicate Gene Plays Essential Roles in Spermatogenesis by Regulating Several Y-Linked Male Fertility Genes

et al. 2010

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Gene duplication is supposed to be the major source for genetic innovations. However, how a new duplicate gene acquires functions by integrating into a pathway and results in adaptively important phenotypes has remained largely unknown. Here, we investigated the biological roles and the underlying molecular mechanism of the young kep1 gene family in the Drosophila melanogaster species subgroup to understand the origin and evolution of new genes with new functions. Sequence and expression analysis demonstrates that one of the new duplicates, nsr (novel spermatogenesis regulator), exhibits positive selection signals and novel subcellular localization pattern. Targeted mutagenesis and whole-transcriptome sequencing analysis provide evidence that nsr is required for male reproduction associated with sperm individualization, coiling, and structural integrity of the sperm axoneme via regulation of several Y chromosome fertility genes post-transcriptionally. The absence of nsr-like expression pattern and the presence of the corresponding cis-regulatory elements of the parental gene kep1 in the pre-duplication species Drosophila yakuba indicate that kep1 might not be ancestrally required for male functions and that nsr possibly has experienced the neofunctionalization process, facilitated by changes of trans-regulatory repertories. These findings not only present a comprehensive picture about the evolution of a new duplicate gene but also show that recently originated duplicate genes can acquire multiple biological roles and establish novel functional pathways by regulating essential genes.

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Section: Resultsmentioning

confidence: 99%

A Young Drosophila Duplicate Gene Plays Essential Roles in Spermatogenesis by Regulating Several Y-Linked Male Fertility Genes

et al. 2010

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“…There were no significant themes among Gene Ontology, phenotype, or in situ annotations for Dm3 and Dm4, besides that their targets seem to be membrane associated (Supplementary Table 2). Earlier genetic and biochemical characterization of Kep1 suggests that it may be involved in regulating splicing (Fruscio et al , 2003; Robard et al , 2006).…”

Section: Resultsmentioning

confidence: 99%

Discovering structural cis ‐regulatory elements by modeling the behaviors of mRNAs

Foat

Stormo

2009

Molecular Systems Biology

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Gene expression is regulated at each step from chromatin remodeling through translation and degradation. Several known RNA-binding regulatory proteins interact with specific RNA secondary structures in addition to specific nucleotides. To provide a more comprehensive understanding of the regulation of gene expression, we developed an integrative computational approach that leverages functional genomics data and nucleotide sequences to discover RNA secondary structuredefined cis-regulatory elements (SCREs). We applied our structural cis-regulatory element detector (StructRED) to microarray and mRNA sequence data from Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens. We recovered the known specificities of Vts1p in yeast and Smaug in flies. In addition, we discovered six putative SCREs in flies and three in humans. We characterized the SCREs based on their condition-specific regulatory influences, the annotation of the transcripts that contain them, and their locations within transcripts. Overall, we show that modeling functional genomics data in terms of combined RNA structure and sequence motifs is an effective method for discovering the specificities and regulatory roles of RNA-binding proteins.

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“…Members of this family have been implicated in the regulation of mRNA translation, mRNA stability, and alternative splicing of premRNA (Baehrecke 1997;Jan et al 1999;Wu et al 2002;Coyle et al 2003;Di Fruscio et al 2003). The STAR/GSG protein GLD-1 is a master regulator of C. elegans germline development; it represses the translation of several key determinants during the spatial and temporal development of the hermaphrodite gonad (Francis et al 1995;Jan et al 1999;Lee and Schedl 2001;Marin and Evans 2003).…”

Section: Discussionmentioning

confidence: 99%

Specificity of the STAR/GSG domain protein Qk1: Implications for the regulation of myelination

Ryder

Williamson²

2004

RNA

110

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Inadequate formation and maintenance of myelin is the basis for several neurodegenerative disorders, including leukodystrophy and multiple sclerosis. In mice, oligodendrocyte differentiation and subsequent formation of myelin requires the Quaking gene. Mutation of this gene leads to embryonic lethality or to a trembling phenotype characteristic of dysmyelination. Quaking encodes Qk1, a member of the highly conserved STAR/GSG family of RNA-binding proteins that function as master developmental regulators in higher eukaryotes. Qk1 has been implicated in the regulation of alternative splicing, stability, and translation control of mRNAs that code for myelin structural components in glial cells. We have used quantitative gel mobility shift and fluorescence polarization assays to define the nucleotide sequence specificity of the Qk1 STAR/GSG domain, and to probe the interaction between Qk1 and the 3-untranslated region (UTR) of myelin basic protein (MBP) mRNA. The results show that Qk1 recognizes a hexanucleotide consensus element that is similar although not identical to the specificity determinant recognized by the Caenorhabditis elegans STAR/GSG protein GLD-1. Several consensus sites are present in the 3-UTR of MBP mRNA. The highest affinity site is located within the RNA localization region, suggesting a possible role for Qk1 in restricting MBP mRNA to the myelin compartment.

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kep1 interacts genetically with dredd / Caspase-8 , and kep1 mutants alter the balance of dredd isoforms

Cited by 21 publications

References 51 publications

A Young Drosophila Duplicate Gene Plays Essential Roles in Spermatogenesis by Regulating Several Y-Linked Male Fertility Genes

A Young Drosophila Duplicate Gene Plays Essential Roles in Spermatogenesis by Regulating Several Y-Linked Male Fertility Genes

Discovering structural cis ‐regulatory elements by modeling the behaviors of mRNAs

Specificity of the STAR/GSG domain protein Qk1: Implications for the regulation of myelination

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