WormBook : the online review of C. elegans biology最新文献

About 70% of C. elegans mRNAs are trans-spliced to one of two 22 nucleotide spliced leaders. SL1 is used to trim off the 5' ends of pre-mRNAs and replace them with the SL1 sequence. This processing event is very closely related to cis-splicing, or intron removal. The SL1 sequence is donated by a 100 nt small nuclear ribonucleoprotein particle (snRNP), the SL1 snRNP. This snRNP is structurally and functionally similar to the U snRNAs (U1, U2, U4, U5 and U6) that play key roles in intron removal and trans-splicing, except that the SL1 snRNP is consumed in the process. More than half of C. elegans pre-mRNAs are subject to SL1 trans-splicing, whereas ~30% are not trans-spliced. The remaining genes are trans-spliced by SL2, which is donated by a similar snRNP, the SL2 snRNP. SL2 recipients are all downstream genes in closely spaced gene clusters similar to bacterial operons. They are transcribed from a promoter at the 5' end of the cluster of between 2 and 8 genes. This transcription makes a polycistronic pre-mRNA that is co-transcriptionally processed by cleavage and polyadenylation at the 3' end of each gene, and this event is closely coupled to the SL2 trans-splicing event that occurs only ~100 nt further downstream. SL2 trans-splicing requires a sequence between the genes, the Ur element, that likely base pairs with the 5' splice site on the SL2 snRNP, in a manner analogous to the interaction between the 5' splice site in cis-splicing with the U1 snRNP. The key difference is that in trans-splicing, the snRNP contains the 5' splice site, whereas in cis-splicing the pre-mRNA does. Some operons, termed "hybrid operons", contain an additional promoter between two genes that can express the downstream gene or genes with a developmental profile that is different from that of the entire operon. The operons contain primarily genes required for rapid growth, including genes whose products are needed for mitochondrial function and the basic machinery of gene expression. Recent evidence suggests that RNA polymerase is poised at the promoters of growth genes, and operons allow more efficient recovery from growth-arrested states, resulting in reduction in the need for this cache of inactive RNA polymerase.

C. elegans feeding depends on the action of the pharynx, a neuromuscular pump that joins the mouth to the intestine. The pharyngeal muscle captures food-bacteria-and transports it back to the intestine. It accomplishes this through a combination of two motions, pumping and isthmus peristalsis. Pumping, the most visible and best understood of the two, is a cycle of contraction and relaxation that sucks in liquid from the surrounding environment along with suspended particles, then expels the liquid, trapping the particles. Pharyngeal muscle is capable of pumping without nervous system input, but during normal rapid feeding its timing is controlled by two pharyngeal motor neuron types. Isthmus peristalsis, a posterior moving wave of contraction of the muscle of the posterior isthmus, depends on a third motor neuron type. Feeding motions are regulated by the presence and quality of food in the worm's environment. Some types of bacteria are better at supporting growth than others. Given a choice, worms are capable of identifying and seeking out higher-quality food. Food availability and quality also affect behavior in other ways. For instance, given all the high-quality food they can eat, worms eventually become satiated, stop eating and moving, and become quiescent.

Alternative splicing is a common mechanism for the generation of multiple isoforms of proteins. It can function to expand the proteome of an organism and can serve as a way to turn off gene expression after transcription. This review focuses on splicing, its regulation and the progress in this field achieved through studies in C. elegans. Recent experiments, including RNA-Seq to uncover and measure the extent of alternative splicing, comparative genomics to identify splicing regulatory elements, and the development of elegant genetic screens using fluorescent reporter constructs, have increased our understanding of the cis-acting sequences that regulate alternative splicing and the trans-acting protein factors that bind to these sequences. The topics covered in this review include constitutive splicing factors, identification of alternatively spliced genes, alternative splicing regulation and the coupling of alternative splicing to nonsense-mediated decay. The significant progress towards uncovering the alternative splicing code in this organism is discussed.

The nervous system represents the most complex tissue of C. elegans both in terms of numbers (302 neurons and 56 glial cells = 37% of the somatic cells in a hermaphrodite) and diversity (118 morphologically distinct neuron classes). The lineage and morphology of each neuron type has been described in detail and neuronal fate markers exists for virtually all neurons in the form of fluorescent reporter genes. The ability to "phenotype" neurons at high resolution combined with the amenability of C. elegans to genetic mutant analysis make the C. elegans nervous system a prime model system to elucidate the nature of the gene regulatory programs that build a nervous system-a central question of developmental neurobiology. Discussing a number of regulatory genes involved in neuronal lineage determination and neuronal differentiation, I will try to carve out in this review a few general principles of neuronal development in C. elegans. These principles may be conserved across phylogeny.

Ethanol is a widely used drug whose mechanism of action, despite intensive study, remains uncertain. Biochemical and electrophysiological experiments have identified receptors and ion channels whose functions are altered at physiological concentrations of ethanol. Yet, the contribution of these potential targets to its intoxicating or behavioral effects is unclear. Unbiased forward genetic screens for resistant or hypersensitive mutants represent an attractive means of identifying the relevant molecular targets or biochemical pathways mediating the behavioral effects of neuroactive compounds. C. elegans has proven to be a particularly useful system for such studies. The behavioral effects of ethanol occur at equivalent tissue concentrations in mammals and in C. elegans, suggesting the existence of conserved drug targets in the nervous system. This chapter reviews the results of studies directed toward determining the mechanisms of action of ethanol. Studies of the neural adaptations that occur with prolonged drug exposure are also discussed. The methods used to characterize the actions of ethanol should be applicable to the characterizations of other compounds that affect the behavior of C. elegans.

An understanding of evolution at the molecular level requires the simultaneous consideration of the 5 fundamental evolutionary processes: mutation, recombination, natural selection, genetic drift, and population dynamic effects. Experimental, comparative genomic, and population genetic work in C. elegans has greatly expanded our understanding of these core processes, as well as of C. elegans biology. This chapter presents a brief overview of some of the most salient features of molecular evolution elucidated by the C. elegans system.

Autophagy is a ubiquitous cellular process responsible for the bulk degradation of cytoplasmic components through an autophagosomal-lysosomal pathway. Genetic screens, primarily in S. cerevisiae, have identified numerous genes that are essential for autophagy. Many of these genes have orthologs in higher eukaryotes, including C. elegans, Drosophila, and mammals. Gene knockdown/knockout studies in C. elegans have been useful to probe the functions of autophagy in an intact multicellular organism that undergoes development to produce different cell types. This review summarizes important themes that have emerged regarding the roles of autophagy in C. elegans in adaptation to stress, aging, normal reproductive growth, cell death, cell growth control, neural synaptic clustering, and the degradation of aggregate-prone proteins.

Caenorhabditis elegans has orthologs for most of the key enzymes involved in eukaryotic intermediary metabolism, suggesting that the major metabolic pathways are probably present in this species. We discuss how metabolic patterns and activity change as the worm traverses development and ages, or responds to unfavorable external factors, such as temperature extremes or shortages in food or oxygen. Dauer diapause is marked by an enhanced resistance to oxidative stress and a shift toward microaerobic and anaplerotic metabolic pathways and hypometabolism, as indicated by the increased importance of the malate dismutation and glyoxylate pathways and the repression of citric acid cycle activity. These alterations promote prolonged survival of the dauer larva; some of these changes also accompany the extended lifespan of insulin/IGF-1 and several mitochondrial mutants. We also present a brief overview of the nutritional requirements, energy storage and waste products generated by C. elegans.