Poly(A)-specific ribonuclease (PARN): An allosterically regulated,processive and mRNA cap-interacting deadenylase

Abstract

Deadenylation of eukaryotic mRNA is a mechanism critical for mRNA function by influencing mRNA turnover and efficiency of protein synthesis. Here, we review poly(A)-specific ribonuclease (PARN), which is one of the biochemically best characterized deadenylases. PARN is unique among the currently known eukaryotic poly(A) degrading nucleases, being the only deadenylase that has the capacity to directly interact during poly(A) hydrolysis with both the m⁷G-cap structure and the poly(A) tail of the mRNA. In short, PARN is a divalent metal-ion dependent poly(A)-specific, processive and cap-interacting 3′–5′ exoribonuclease that efficiently degrades poly(A) tails of eukaryotic mRNAs. We discuss in detail the mechanisms of its substrate recognition, catalysis, allostery and processive mode of action. On the basis of biochemical and structural evidence, we present and discuss a working model for PARN action. Models of regulation of PARN activity by trans-acting factors are discussed as well as the physiological relevance of PARN.     

The science of plant morphology: definition, history, and role in modern biology

As a scientific discipline, plant morphology is 211 yr old, originated by Goethe in 1790. It is a discipline that has largely been Germanic in practice. Because it took its origins from the study of the natural history of plants and the United States is principally an engineering society, the discipline of plant morphology in its pure form has never been widely practiced in this country. What has been labeled "plant morphology" in the United States has served largely as a handmaiden for systematics, using morphological characteristics to carve up diversity into its systematic subunits. Because the heart of plant morphology as a science is a focus on the convergences rather than the homologies in a phylogenetic sense, the German tradition of plant morphology is a unifying science that focuses on fundamental themes that transcend systematic boundaries. This paper traces the history of the science of plant morphology through the lineage of its principal practitioners: Goethe, Hofmeister, von Goebel, and Troll. It also evaluates the principles of plant morphology by applying them to the phyletically diverse Pteridophytes, showing that contemporary members of that group exhibit levels of shoot organization comparable to that of seed plants and discusses the implications of these findings.     

The oligo(A) tail on histone mRNA plays an active role in translational silencing of histone mRNA during Xenopus oogenesis

Metazoan replication-dependent histone mRNAs end in a stem-loop sequence. The one known exception is the histone mRNA in amphibian oocytes, which has a short oligo(A) tail attached to the stem-loop sequence. Amphibian oocytes also contain two proteins that bind the 3' end of histone mRNA: xSLBP1, the homologue of the mammalian SLBP, and xSLBP2, which is present only in oocytes. xSLBP2 is an inhibitor of histone mRNA translation, while xSLBP1 activates translation. The short A tail on histone mRNAs appears at stage II to III of oogenesis and is present on histone mRNAs throughout the rest of oogenesis. At oocyte maturation, the oligo(A) tail is removed and the xSLBP2 is degraded, resulting in the activation of translation of histone mRNA. Both SLBPs bind to the stem-loop with the oligo(A) tail with similar affinities. Reporter mRNAs ending in the stem-loop with or without the oligo(A) tail are translated equally well in a reticulocyte lysate, and their translation is stimulated by the presence of xSLBP1. In contrast, translation of the reporter mRNA with an oligo(A) tail is not activated in frog oocytes in response to the presence of xSLBP1. These results suggest that the oligo(A) tail is an active part of the translation repression mechanism that silences histone mRNA during oogenesis and that its removal is part of the mechanism that activates translation.     

The mechanism and regulation of deadenylation: identification and characterization of Xenopus PARN.

In Xenopus oocytes, the deadenylation of a specific class of maternal mRNAs results in their translational repression. Here we report the purification, characterization, and molecular cloning of the Xenopus poly(A) ribonuclease (xPARN). xPARN copurifies with two polypeptides of 62 kDa and 74 kDa, and we provide evidence that the 62-kDa protein is a proteolytic product of the 74-kDa protein. We have isolated the full-length xPARN cDNA, which contains the tripartite exonuclease domain conserved among RNase D family members, a putative RNA recognition motif, and a domain found in minichromosome maintenance proteins. Characterization of the xPARN enzyme shows that it is a poly(A)-specific 3' exonuclease but does not require an A residue at the 3' end. However, the addition of 25 nonadenylate residues at the 3' terminus, or a 3' terminal phosphate is inhibitory. Western analysis shows that xPARN is expressed throughout early development, suggesting that it may participate in the translational silencing and destabilization of maternal mRNAs during both oocyte maturation and embryogenesis. In addition, microinjection experiments demonstrate that xPARN can be activated in the oocyte nucleus in the absence of cytoplasmic components and that nuclear export of deadenylated RNA is impeded. Based on the poly(A) binding activity of xPARN in the absence of catalysis, a model for substrate specificity is proposed.     

Insect-repelling behaviour in bovids: role of mass, tail length, and group size

Biting insects are costly to hosts, and insect-repelling movements of the tail, ears, head, and feet are widespread in mammals and effective in reducing bites. We investigate whether the 'peripheral stimulation model' can explain the regulation of this widespread behaviour pattern in a comparative study of bovids. The peripheral stimulation hypothesis predicts: (1) a positive association between insect-repelling rates and body size because larger hosts produce more of the sensory cues that attract biting insects; (2) that individuals in larger groups will exhibit a higher rate of insect defense behaviour if group size and insect attraction follows a linear function; and (3) larger species will evolve proportionately longer tails in response to higher rates of insect attack. To test these predictions, we observed insect-repelling behaviour in 26 species of bovids at a zoological park, and controlled for common ancestry with formal phylogenetic analyses (independent contrasts). Consistent with the peripheral stimulation hypothesis, rates of tail-switching and all insect-repelling behaviours combined were positively associated with body mass, whereas ear-flicking was positively associated with proportional tail length. Larger bovids had proportionately longer tails for more effective fly swatting. There was no significant association between insect-repelling rate and group size, suggesting that a nonlinear relationship exists between group size and insect attacks whereby individuals in larger groups do not experience an increased attack rate.  © 2007 The Linnean Society of London, Biological Journal of the Linnean Society , 2007, 91 , 383–392.     

Save your gut save your age: The role of the microbiome in stem cell ageing

The tremendous importance of microbiota in microbial homoeostasis, alterations in metabolism and both innate and adaptive immune systems has been well established. A growing body of evidence support that dysbiosis or compositional changes in gut microbiota is linked to the ageing of stem cells in terms of dysregulations of metabolism, aberrant activation of the immune system as well as promoting epigenetic instability of stem cell. In this concise review, we elucidate recent emerging topics on microbiotic alterations and underlying mechanisms in stem cell ageing.     

The role of pheromones in tick biology

Ticks are important vectors of pathogens that cause human and animal disease. Pheromones play a role of fundamental importance in intraspecies communication. Here, Gordon Hamilton discusses how these chemical messengers play a role in mate location, host location, and survival in adverse conditions, and how manipulation of this chemical communication system may provide a potential method of tick control.     

The Kiss of Death: Chagas Disease in the Americas

The Kiss of Death: Chagas Disease in the Americas. Joseph William Bastien. Salt Lake City: University of Utah Press. 1998. 301 pp.     

Character identification in evolutionary biology: The role of the organism

Summary In this article we argue that an organismic perspective in character identification can alleviate a structural deficiency of mathematical models in biology relative to the ones in the physical sciences. The problem with many biological theories is that they do not contain the conditions of their validity or a method of identifying objects that are appropriate instances of the models. Here functionally important biological characters are introduced as conceptual abstractions derived within the context of an ontologically prior object, such as a cell or an organism. To illustrate this approach, we present an analytical method of character decomposition based on the notion of the quasi-independence of traits. Two cases are analyzed: context dependent units of inheritance and a model of character identification in adaptive evolution. We demonstrate that in each case the biological process as represented by a mathematical theory entails the conditions for the individualization of characters. Our approach also requires a conceptual re-orientation in the way we build biological models. Rather than defining a set of biological characters a priori, functionally relevant characters are identified in the context of a higher level biological process.     

The role of protease activity in ErbB biology

Proteases are now recognized as having an active role in a variety of processes aside from their recognized metabolic role in protein degradation. Within the ErbB system of ligands and receptors, proteases are known to be necessary for the generation of soluble ligands from transmembrane precursors and for the processing of the ErbB4 receptor, such that its intracellular domain is translocated to the nucleus. There are two protease activities involved in the events: proteases that cleave within the ectodomain of ligand (or receptor) and proteases that cleave the substrate within the transmembrane domain. The former are the ADAM proteases and the latter are the γ-secretase complex and the rhomboid proteases. This review discusses the roles of each of these protease systems within the ErbB system.     

The role of ADAM-mediated shedding in vascular biology

Within the vasculature the disintegrins and metalloproteinases (ADAMs) 8, 9, 10, 12, 15, 17, 19, 28 and 33 are expressed on endothelial cells, smooth muscle cells and on leukocytes. As surface-expressed proteases they mediate cleavage of vascular surface molecules at an extracellular site close to the membrane. This process is termed shedding and leads to the release of a soluble substrate ectodomain thereby critically modulating the biological function of the substrate. In the vasculature several surface molecules undergo ADAM-mediated shedding including tumour necrosis factor (TNF) α, interleukin (IL) 6 receptor α, L-selectin, vascular endothelial (VE)-cadherin, the transmembrane CX3C-chemokine ligand (CX3CL) 1, Notch, transforming growth factor (TGF) and heparin-binding epidermal growth factor (HB-EGF). These substrates play distinct roles in vascular biology by promoting inflammation, permeability changes, leukocyte recruitment, resolution of inflammation, regeneration and/or neovascularisation. Especially ADAM17 and ADAM10 are capable of cleaving many substrates with diverse function within the vasculature, whereas other ADAMs have a more restricted substrate range. Therefore, targeting ADAM17 or ADAM10 by pharmacologic inhibition or gene knockout not only attenuates the inflammatory response in animal models but also affects tissue regeneration and neovascularisation. Recent discoveries indicate that other ADAMs (e.g. ADAM8 and 9) also play important roles in vascular biology but appear to have more selective effects on vascular responses (e.g. on neovascularisation only). Although, targeting of ADAM17 and ADAM10 in inflammatory diseases is still a promising approach, temporal and spatial as well as substrate-specific inhibition approaches are required to minimise undesired side effects on vascular cells.