A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans

Wang, Liaoteng; Eckmann, Christian R.; Kadyk, Lisa C.; Wickens, Marvin; Kimble, Judith

doi:10.1038/nature01039

Cited by 278 publications

(394 citation statements)

References 27 publications

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“…These data were not surprising, since conserved domain analysis showed that, similar to hmtPAP and other members of the novel PAP family, kPAP2 lacks RNA-binding domains. Therefore, the presence of a bridging partner that can mediate RNA substrate-kPAP2 interaction might be required in the assay for kPAP2 to perform its enzymatic activity, resembling the model for the novel cytoplasmic PAP, GLD-2, in C. elegans (31). kPAP2 associated proteins would necessarily be absent from reactions with recombinant or in vitro transcribed/translated enzyme.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a new class of PAPs was described in several eukaryotes. Members of this class include Cid1p and Cid13p in the fission yeast Schizosaccharomyces pombe (29,30), GLD-2 in Caenorhabditis elegans (31), and hmtPAP in human mitochondria (11,12). Members of this novel PAP family diverge from canonical PAPs, exhibiting relatively low homology within the catalytic domain.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, in order for members of this novel PAP family to execute their function, the existence of an associated RNA-binding protein as part of its functional moiety can be postulated. Indeed, Wang et al have reported that in C. elegans, an RNA-binding protein termed GLD-3 binds to and stimulates the polyadenylation activity of GLD-2 (31). Another member of the novel PAP family, hmtPAP, has been shown to be the bona fide mitochondrial PAP in humans (11,12).…”

Section: Introductionmentioning

confidence: 99%

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Targeted depletion of a mitochondrial nucleotidyltransferase suggests the presence of multiple enzymes that polymerize mRNA 3′ tails in Trypanosoma brucei mitochondria

Kao

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2007

Molecular and Biochemical Parasitology

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Polyadenylation plays an important role in regulating RNA stability in Trypanosoma brucei mitochondria. To date, little is known about the enzymes responsible for the addition of mRNA 3′ tails in this system. In this study, we characterize a trypanosome homolog of the human mitochondrial poly(A) polymerase, which we term kPAP2. kPAP2 is mitochondrially localized and expressed in both bloodstream and procyclic form trypanosomes. Targeted gene depletion using RNAi showed that kPAP2 is not required for T. brucei growth in either bloodstream or procyclic life stages, nor is it essential for differentiation from bloodstream to procyclic form. We also demonstrate that steady state abundance of several mitochondrial RNAs was largely unaffected upon kPAP2 downregulation. Interestingly, mRNA 3′ tail analysis of several mRNAs from both life cycle stages in uninduced kPAP2 RNAi cells demonstrated that tail length and uridine content are both regulated in a transcript-specific manner. mRNA-specific tail lengths were maintained upon kPAP2 depletion. However, the percentage of uridine residues in 3′ tails was increased, and conversely the percentage of adenosine residues was decreased, in a distinct subset of mRNAs when kPAP2 levels were downregulated. Thus, kPAP2 apparently contributes to the incorporation of adenosine residues in 3′ tails of some, but not all, mitochondrial mRNAs. Together, these data suggest that multiple nucleotidyltransferases act on mitochondrial mRNA 3′ ends, and that these enzymes are somewhat redundant and subject to complex regulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeted depletion of a mitochondrial nucleotidyltransferase suggests the presence of multiple enzymes that polymerize mRNA 3′ tails in Trypanosoma brucei mitochondria

Kao

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2007

Molecular and Biochemical Parasitology

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“…Another component of the GLD-1 pathway is NOS-3 (Hansen et al, 2004a). The GLD-2 pathway includes the GLD-2 cytoplasmic poly(A) polymerase (Wang et al, 2002) and GLD-3, an RNA-binding protein (Eckmann et al, 2004). It remains unclear how the regulatory activities of these pathways specifically promote the meiotic cell fate.…”

Section: Introductionmentioning

confidence: 99%

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

et al. 2011

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SUMMARYThe C. elegans germline provides an excellent model for analyzing the regulation of stem cell activity and the decision to differentiate and undergo meiotic development. The distal end of the adult hermaphrodite germline contains the proliferative zone, which includes a population of mitotically cycling cells and cells in meiotic S phase, followed by entry into meiotic prophase. The proliferative fate is specified by somatic distal tip cell (DTC) niche-germline GLP-1 Notch signaling through repression of the redundant GLD-1 and GLD-2 pathways that promote entry into meiosis. Here, we describe characteristics of the proliferative zone, including cell cycle kinetics and population dynamics, as well as the role of specific cell cycle factors in both cell cycle progression and the decision between the proliferative and meiotic cell fate. Mitotic cell cycle progression occurs rapidly, continuously, with little or no time spent in G1, and with cyclin E (CYE-1) levels and activity high throughout the cell cycle. In addition to driving mitotic cell cycle progression, CYE-1 and CDK-2 also play an important role in proliferative fate specification. Genetic analysis indicates that CYE-1/CDK-2 promotes the proliferative fate downstream or in parallel to the GLD-1 and GLD-2 pathways, and is important under conditions of reduced GLP-1 signaling, possibly corresponding to mitotically cycling proliferative zone cells that are displaced from the DTC niche. Furthermore, we find that GLP-1 signaling regulates a third pathway, in addition to the GLD-1 and GLD-2 pathways and also independent of CYE-1/CDK-2, to promote the proliferative fate/inhibit meiotic entry.

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“…3; Kadyk and Kimble, 1998;Hansen et al, 2004a,b). Two of these redundant pathways are defined by the activities of GLD-1, a KH-domain containing RNA-binding protein (Francis et al, 1995) and the GLD-2 cytoplasmic poly-A polymerase protein (Wang et al, 2002) that acts in a complex with GLD-3, a Bicaudal C-related protein Eckmann et al, 2002Eckmann et al, , 2004. The GLD-1 and GLD-2 pathways are not only redundant for meiotic entry, they also interact, forming a complex genetic regulatory network.…”

Section: Glp-1/notch Signaling and The Proliferative Zonementioning

confidence: 99%

Caenorhabditis elegans germ line: A model for stem cell biology

Hubbard

2007

Developmental Dynamics

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A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans

Cited by 278 publications

References 27 publications

Targeted depletion of a mitochondrial nucleotidyltransferase suggests the presence of multiple enzymes that polymerize mRNA 3′ tails in Trypanosoma brucei mitochondria

Targeted depletion of a mitochondrial nucleotidyltransferase suggests the presence of multiple enzymes that polymerize mRNA 3′ tails in Trypanosoma brucei mitochondria

Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

Caenorhabditis elegans germ line: A model for stem cell biology

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