Early sensory processing can play a critical role in sensing environmental cues. We have investigated the physiological and behavioral function of gain control at the first synapse of olfactory processing in Drosophila. We report that olfactory receptor neurons (ORNs) express the GABAB receptor (GABABR) and its expression expands the dynamic range of ORN synaptic transmission that is preserved in projection neuron responses. Strikingly, we find that different ORN channels have unique baseline levels of GABABR expression. ORNs that sense the aversive odorant CO2 do not express GABABRs nor exhibit any presynaptic inhibition. In contrast, pheromone-sensing ORNs express a high level of GABABRs and exhibit strong presynaptic inhibition. Furthermore, a behavioral significance of presynaptic inhibition was revealed by a courtship behavior in which pheromone-dependent mate localization is impaired in flies that lack GABABRs in specific ORNs. Together, these findings indicate that different olfactory receptor channels may employ heterogeneous presynaptic gain control as a mechanism to allow an animal’s innate behavioral responses to match its ecological needs.
Nuclear factor of activated T cells (NFAT) is a calcium-responsive transcription factor. We describe here an NFAT-based neural tracing method—CaLexA (calcium-dependent nuclear import of Lex A)—for labeling active neurons in behaving animals. In this system, sustained neural activity induces nuclear import of the chimeric transcription factor LexA-VP16-NFAT, which in turn drives green fluorescent protein (GFP) reporter expression only in active neurons. We tested this system in Drosophila and found that volatile sex pheromones excite specific neurons in the olfactory circuit. Furthermore, complex courtship behavior associated with multi-modal sensory inputs activated neurons in the ventral nerve cord. This method harnessing the mechanism of activity-dependent nuclear import of a transcription factor can be used to identify active neurons in specific neuronal population in behaving animals.
Different RNA species are exported from the nucleus by distinct mechanisms. Among the different RNAs, mRNAs and major spliceosomal U snRNAs share several structural similarities, yet they are exported by distinct factors. We previously showed that U1 snRNAs behaved like an mRNA in nuclear export if various ∼300-nucleotide fragments were inserted in a central position. Here we show that this export switch is dependent on the length of the insertion but independent of its position, indicating unequivocally that this switch is indeed the result of RNA length. We also show that intronless mRNAs can be progressively converted to use the U snRNA export pathway if the mRNAs are progressively shortened by deletion. In addition, immunoprecipitation experiments show that the protein composition of export RNPs is influenced by RNA length. These findings indicate that RNA length is one of the key determinants of the choice of RNA export pathway. Based on these results and previous observations, a unified model of how an RNA is committed to a specific export pathway is proposed.[Keywords: RNA export; mRNA; U snRNA; RNA length] Supplemental material is available at http://www.genesdev.org.
Intron-containing pre-mRNAs are normally retained in the nucleus until they are spliced to produce mature mRNAs that are exported to the cytoplasm. Although the detailed mechanism is not well understood, the formation of splicing-related complexes on premRNAs is thought to be responsible for the nuclear retention. Therefore, pre-mRNAs containing suboptimal splice sites should tend to leak out to the cytoplasm. Such pre-mRNAs often contain purine-rich exonic splicing enhancers (ESEs) that stimulate splicing of the adjacent intron. Here, we show that ESEs per se possess an activity to retain RNAs in the nucleus through a saturable nuclear retention factor. Cross-competition experiments revealed that intron-containing pre-mRNAs (without ESEs) used the same saturable nuclear retention factor as ESEs. Interestingly, although intronless mRNAs containing ESEs were also poorly exported, spliced mRNAs produced from ESE-containing pre-mRNAs were efficiently exported to the cytoplasm. Thus, the splicing reaction can reset the nuclear retention state caused by ESEs, allowing nuclear export of mature mRNAs. Our results reveal a novel aspect of ESE activity that should contribute to gene expression and RNA quality control.nuclear export ͉ quality control T he nuclear envelope separates eukaryotic cells into two major compartments, the nucleus and the cytoplasm. This compartmentalization necessitates transport through the nuclear pore complexes, the channels for material exchange across the nuclear envelope barrier (reviewed in ref. 1). The vast majority of RNA species, after their synthesis and processing in the nucleus, are exported to the cytoplasm. Some specific RNA species, however, are not exported but instead stay in the nucleus. Such RNAs include U6 small nuclear RNAs (snRNAs), small nucleolar RNAs, small Cajal body RNAs, some mRNA-like noncoding RNAs, inosinecontaining RNAs, and various unprocessed immature RNAs (reviewed in refs. 2-6). Among them, intron-containing pre-mRNAs are retained in the nucleus as a part of the RNA quality-control mechanism that ensures appearance in the cytoplasm of only mature mRNAs. This retention is thought to be achieved as a result of the formation of splicing-related complexes, although the detailed mechanism is not well understood (reviewed in refs. 6 and 7).Properly processed RNAs are generally exported to the cytoplasm, but different RNA species, such as tRNAs, U snRNAs, mRNAs, and rRNAs, use distinct export pathways, i.e., distinct sets of export factors (reviewed in ref. 8). Accumulating evidence shows that the pathway of RNA export can influence the fate of a given RNA in the cytoplasm (8), indicating the biological importance of the choice of RNA export pathway. This means that the cellular export machinery must be able to discriminate distinct RNA species, and therefore each RNA species should have its own distinguishing features.We have been searching for the distinguishing features of mRNA, termed mRNA ID elements. We previously found that the presence of introns in mRNA prec...
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