It is poorly understood how sensory systems memorize the intensity of sensory stimulus, compare it with a newly sensed stimulus, and regulate the orientation behaviour based on the memory. Here we report that Caenorhabditis elegans memorizes the environmental salt concentration during cultivation and exhibits a strong behavioural preference for this concentration. The right-sided amphid gustatory neuron known as ASER, senses decreases in salt concentration, and this information is transmitted to the postsynaptic AIB interneurons only in the salt concentration range lower than the cultivation concentration. In this range, animals migrate towards higher concentration by promoting turning behaviour upon decreases in salt concentration. These observations provide a mechanism for adjusting the orientation behaviour based on the memory of sensory stimulus using a simple neural circuit. A ll living animals are endowed with the capacity to seek optimal ambient conditions. Such behaviour requires memorizing the intensity of sensory stimulus associated with favourable conditions, recognizing the spatio-temporal changes of the stimulus intensity under current conditions, comparing it with the memorized stimulus intensity and regulating the motor output to generate a movement towards a preferred direction. However, in most sensory systems how stimulus intensity is memorized and how distinct orientation behaviours are generated depending on the memory have been poorly explored.Sodium chloride was identified as a chemoattractant for C. elegans 1 . Based on this view the mechanisms of salt chemotaxis has been examined for decades. Amphid taste neurons ASE, which consist of two morphologically symmetric neurons on the left (ASEL) and the right (ASER), have a predominant role in chemotaxis to NaCl and other inorganic salts 2-4 . Calcium imaging experiments showed that these neurons are functionally asymmetric: ASER is depolarized by decreases in salt concentration, while ASEL responds to increases 5 . As activation of ASER and ASEL promotes redirecting turns and forward locomotion, respectively, it was suggested that the right and the left neurons have distinct roles but act in concert for migrating up salt gradient 5 . Through another line of studies on the migration behaviours, two distinct behavioural mechanisms that drive animals towards higher salt concentration have been characterized so far (see below) 6,7 . Despite these sets of knowledge, the physiological and mechanistic properties of the information flow for salt chemotaxis downstream of the sensory neurons have not been obvious, as ASEL and ASER form synapses onto overlapping targets (Fig. 1a).Meanwhile, we have previously shown that pairing starvation with exposure to NaCl causes salt avoidance learning in C. elegans 8 . The insulin signalling pathway components, DAF-2 insulin receptor, AGE-1 phosphoinositide 3-kinase and AKT-1 AKT kinase, are required in ASER for this learning 9 . Activation of the Gq/DAG/PKC signalling pathway consisting of EGL-30 Gq, diacylglycer...

A number of meiosis-specific mRNAs are initially weakly transcribed, but then selectively removed during fission yeast mitotic growth. These mRNAs harbour a region termed DSR (determinant of selective removal), which is recognized by the YTH family RNA-binding protein Mmi1p. Mmi1p directs the destruction of these mRNAs in collaboration with nuclear exosomes. However, detailed molecular mechanisms underlying this process of selective mRNA elimination have remained elusive. In this study, we demonstrate the critical role of polyadenylation in this process. Two-hybrid and genetic screens revealed potential interactions between Mmi1p and proteins involved in polyadenylation. Additional investigations showed that destruction of DSR-containing mRNAs by exosomes required polyadenylation by a canonical poly(A) polymerase. The recruitment of Pab2p, a poly(A)-binding protein, to the poly(A) tail was also necessary for mRNA destruction. In cells undergoing vegetative growth, Mmi1p localized with exosomes, Pab2p, and components of the polyadenylation complex in several patchy structures in the nucleoplasm. These patches may represent the sites for degradation of meiosis-specific mRNAs with untimely expression.

A number of meiosis-specific transcripts are selectively eliminated during the mitotic cell cycle in fission yeast. Mmi1, an RNA-binding protein, plays a crucial role in this selective elimination. Mmi1 recognizes a specific region, namely, the determinant of selective removal (DSR) on meiotic transcripts and induces nuclear exosome-mediated elimination. During meiosis, Mmi1 is sequestered by a chromosome-associated dot structure, Mei2 dot, allowing meiosis-specific transcripts to be stably expressed. Red1, a zinc-finger protein, is also known to participate in the Mmi1/DSR elimination system, although its molecular function has remained elusive. To uncover the detailed molecular mechanisms underlying the Mmi1/DSR elimination system, we sought to identify factors that interact genetically with Mmi1. Here, we show that one of the identified factors, Iss10, is involved in the Mmi1/DSR system by regulating the interaction between Mmi1 and Red1. In cells lacking Iss10, association of Red1 with Mmi1 is severely impaired, and target transcripts of Mmi1 are ectopically expressed in the mitotic cycle. During meiosis, Iss10 is downregulated, resulting in dissociation of Red1 from Mmi1 and subsequent suppression of Mmi1 activity.