Fragile X mental retardation gene (FMR1) encodes an RNA binding protein that acts as a negative translational regulator. We have developed a Drosophila fragile X syndrome model using loss-of-function mutants and overexpression of the FMR1 homolog (dfxr). dfxr nulls display enlarged synaptic terminals, whereas neuronal overexpression results in fewer and larger synaptic boutons. Synaptic structural defects are accompanied by altered neurotransmission, with synapse type-specific regulation in central and peripheral synapses. These phenotypes mimic those observed in mutants of microtubule-associated Futsch. Immunoprecipitation of dFXR shows association with futsch mRNA, and Western analyses demonstrate that dFXR inversely regulates Futsch expression. dfxr futsch double mutants restore normal synaptic structure and function. We propose that dFXR acts as a translational repressor of Futsch to regulate microtubule-dependent synaptic growth and function.

While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X normal coverage), we identified structural variants altering critical regulators of tumorigenesis and progression not detectable by exome approaches. Notably, we observed amplification of an intergenic enhancer region 624 kb upstream of the androgen receptor (AR) in 81% of patients, correlating with increased AR expression. Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer.

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hairy (A) acts as a negative regulator in both embryonic segmentation and adult peripheral nervous system (PNS) development in Drosophila. Here, we demonstrate that h, a basic-helix-loop-helix (bHLH) protein, is a sequence-specific DNA-binding protein and transcriptional repressor. We identify the proneural gene acbaete

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SUMMARYIn plants, the ERF/EREBP family of transcriptional regulators plays a key role in adaptation to various biotic and abiotic stresses. These proteins contain a conserved AP2 DNA-binding domain and several uncharacterized motifs. Here, we describe a short motif, termed 'EDLL', that is present in AtERF98/TDR1 and other clade members from the same AP2 sub-family. We show that the EDLL motif, which has a unique arrangement of acidic amino acids and hydrophobic leucines, functions as a strong activation domain. The motif is transferable to other proteins, and is active at both proximal and distal positions of target promoters. As such, the EDLL motif is able to partly overcome the repression conferred by the AtHB2 transcription factor, which contains an ERF-associated amphiphilic repression (EAR) motif. We further examined the activation potential of EDLL by analysis of the regulation of flowering time by NF-Y (nuclear factor Y) proteins. Genetic evidence indicates that NF-Y protein complexes potentiate the action of CONSTANS in regulation of flowering in Arabidopsis; we show that the transcriptional activation function of CONSTANS can be substituted by direct fusion of the EDLL activation motif to NF-YB subunits. The EDLL motif represents a potent plant activation domain that can be used as a tool to confer transcriptional activation potential to heterologous DNA-binding proteins.

authors note errors in three sentences in the second paragraph on page 15042, left column. The corrected paragraph is reprinted below, and the revised sentences appear in boldface. The authors are grateful to Dr. Benny Abraham for identifying the errors.The reported SNP for CD24 is a replacement of C at nucleotide 226 by T (C3T) in the coding region of exon 2 (GenBank accession no. NM013230), which results in a substitution of Ala at amino acid 57 by Val near the GPI anchorage site of the mature protein. The genomic DNA was isolated from Ϸ5 ϫ 10 6 human peripheral blood leukocytes (PBL) by using the QIAamp DNA Blood Minikit (Qiagen, Valencia, CA). DNA fragments bearing this SNP site were amplified by PCR by using a forward primer (TTG TTG CCA CTT GGC ATT TTT GAG GC) and a reverse primer (GGA TTG GGT TTA GAA GAT GGG GAA A). The PCR conditions were as follows: 94°C for 1 min, 50°C for 1 min, and 72°C for 1 min, for 35 cycles. The predicted CD24 PCR fragment is 453 bp long. The C3T change yielded a BstXI restriction enzyme site at nucleotide 225, which allowed us to differentiate these two different CD24 alleles by restriction fragment length polymorphism analysis. Briefly, an aliquot of CD24 PCR products was digested with BstXI for 16 h at 50°C. The digested products were then separated in a 2.5% agarose gel. The predicted digestion pattern is as follows: PCR products of T226 allele will be cut into two small fragments (325 and 129 bp), whereas those of the C226 will be completely resistant. A combination of the two types of the products at close to 50% levels indicates the heterozygosity of the subject. 1073͞pnas.0501422102), the authors note the following regarding the homology of conceptual translations of putative noncoding RNA (pncr) transcripts to known proteins. The report correctly states that for all candidate noncoding transcripts curated in this study, BLASTX analyses using default parameters return no results. However, subsequent analyses of those candidates designated by this study as pncr genes using BLASTP with a PAM30 substitution matrix has revealed homology to known proteins for 2 of the 17 genes listed in Table 2: pncr005:2R and pncr006:X. Homology to a conceptual translation was found for a third transcript, pncr007:3R. We are therefore withdrawing the pncr gene designations in these three cases. No protein homology is detected for other pncr transcripts under these parameters.