DDX3 participates in miRNA biogenesis and RNA interference through translational control of PACT and interaction with AGO2.

DDX3 is a DEAD-box RNA helicase that plays multiple roles in RNA metabolism, including translation. We previously reported that DDX3 is required for translation of PACT, a binding partner of Dicer, suggesting a role for DDX3 in microRNA (miRNA) biogenesis and RNA interference (RNAi). Emerging evidence suggests that DDX3 plays a vital role in tumorigenesis and cancer progression, however, its underlying mechanism is still not fully understood.

hnRNP Q/SYNCRIP interacts with LIN28B and modulates the LIN28B/let-7 axis in human hepatoma cells.

The RNA-binding protein LIN28B represses the biogenesis of the tumor suppressor let-7. The LIN28B/let-7 axis regulates cell differentiation and is associated with various cancers. The RNA-binding protein Q (hnRNP Q) or SYNCRIP (Synaptotagmin Binding Cytoplasmic RNA Interacting Protein) has been implicated in mRNA splicing, mRNA transport, translation, and miRNAs biogenesis as well as metabolism in cancer.

TIAM-1 differentially regulates dendritic and axonal microtubule organization in patterning neuronal development through its multiple domains.

Axon and dendrite development require the cooperation of actin and microtubule cytoskeletons. Microtubules form a well-organized network to direct polarized trafficking and support neuronal processes formation with distinct actin structures. However, it is largely unknown how cytoskeleton regulators differentially regulate microtubule organization in axon and dendrite development.

Transgenic refractory Aedes aegypti lines are resistant to multiple serotypes of dengue virus.

The areas where dengue virus (DENV) is endemic have expanded rapidly, driven in part by the global spread of Aedes species, which act as disease vectors. DENV replicates in the mosquito midgut and is disseminated to the mosquito's salivary glands for amplification. Thus, blocking virus infection or replication in the tissues of the mosquito may be a viable strategy for reducing the incidence of DENV transmission to humans.

phiC31 integrase for recombination-mediated single-copy insertion and genome manipulation in Caenorhabditis elegans.

Caenorhabditis elegans benefits from a large set of tools for genome manipulation. Yet, the precise single-copy insertion of very large DNA constructs (>10 kb) and the generation of inversions are still challenging. Here, we adapted the phiC31 integrase system for C.

Loss of Fis1 impairs proteostasis during skeletal muscle aging in Drosophila.

Increased levels of dysfunctional mitochondria within skeletal muscle are correlated with numerous age-related physiopathological conditions. Improving our understanding of the links between mitochondrial function and muscle proteostasis, and the role played by individual genes and regulatory networks, is essential to develop treatments for these conditions. One potential player is the mitochondrial outer membrane protein Fis1, a crucial fission factor heavily involved in mitochondrial dynamics in yeast but with an unknown role in higher-order organisms.

dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations.

To maintain a particular cell fate, a unique set of genes should be expressed while another set is repressed. One way to repress gene expression is through Polycomb group (PcG) proteins that compact chromatin into a silent configuration. In addition to cell fate maintenance, PcG proteins also maintain normal cell physiology, for example cell cycle.

Genetic control of nucleolar size: An evolutionary perspective.

Exploiting a C. elegans mutant (ncl-1) exhibiting nucleolar abnormalities, we recently identified the let-7/ncl-1/fib-1 genetic cascade underlying proper rRNA abundance and nucleolar size. These 3 factors, let-7 (a miRNA), NCL-1 (a member of the TRIM-NHL family), and fibrillarin (a nucleolar methyltransferase), are evolutionarily conserved across metazoans.

A novel function for the DEAD-box RNA helicase DDX-23 in primary microRNA processing in Caenorhabditis elegans.

Primary microRNAs (pri-miRNAs) are cleaved by the nuclear RNase III Drosha to produce hairpin-shaped precursor miRNAs (pre-miRNAs). In humans, this process is known to be facilitated by the DEAD-box helicases p68 (DDX5) and p72 (DDX17). In this study, we performed a candidate-based RNAi screen in C.

A Genetic Cascade of let-7-ncl-1-fib-1 Modulates Nucleolar Size and rRNA Pool in Caenorhabditis elegans.

Ribosome biogenesis takes place in the nucleolus, the size of which is often coordinated with cell growth and development. However, how metazoans control nucleolar size remains largely unknown. Caenorhabditis elegans provides a good model to address this question owing to distinct tissue distribution of nucleolar sizes and a mutant, ncl-1, which exhibits larger nucleoli than wild-type worms.

BCAS2 Regulates Delta-Notch Signaling Activity through Delta Pre-mRNA Splicing in Drosophila Wing Development.

Previously, we showed that BCAS2 is essential for Drosophila viability and functions in pre-mRNA splicing. In this study, we provide strong evidence that BCAS2 regulates the activity of Delta-Notch signaling via Delta pre-mRNA splicing. Depletion of dBCAS2 reduces Delta mRNA expression and leads to accumulation of Delta pre-mRNA, resulting in diminished transcriptions of Delta-Notch signaling target genes, such as cut and E(spl)m8.

RACK-1 regulates let-7 microRNA expression and terminal cell differentiation in Caenorhabditis elegans.

The let-7 microRNA (miRNA) regulates cell cycle exit and terminal differentiation in the C. elegans heterochronic gene pathway. Low expression of let-7 results in retarded vulva and hypodermal cell development in C.

Ribosomal protein RPS-14 modulates let-7 microRNA function in Caenorhabditis elegans.

The let-7 microRNA (miRNA) regulates developmental timing at the larval-to-adult transition in Caenorhabditis elegans. Dysregulation of let-7 results in irregular hypodermal and vulval development. Disrupted let-7 function is also a feature of human lung cancer.

Identification of specific let-7 microRNA binding complexes in Caenorhabditis elegans.

Little is known about the protein complexes required for microRNA formation and function. Here we used native gel electrophoresis to identify miRNA ribonucleoprotein complexes (miRNPs) in Caenorhabditis elegans. Our data reveal multiple distinct miRNPs that assemble on the let-7 miRNA in vitro.

And now introducing mammalian mirtrons.

Mirtrons are short hairpin introns recently found in flies and nematodes that provide an alternative source for animal microRNA biogenesis and use the splicing machinery to bypass Drosha cleavage in initial maturation. The presence of mirtrons outside of invertebrates was not previously known. In the October 26 issue of Molecular Cell, Berezikov et al.

microRNA-mediated silencing inside P-bodies.

Cytoplasmic processing bodies, or P-bodies, contain a high concentration of enzymes and factors required for mRNA turnover and translational repression. Recent studies provide evidence that the mRNAs silenced by miRNAs are localized to P-bodies for storage or degradation, perhaps in adjacent subcompartments. mRNP remodeling, potentially induced by miRISC or RNA helicase activity, may cause the modification of the translation initiation complex at the 5' end of mRNA, following translational repression and localization to P-bodies.

Functional links between the Prp19-associated complex, U4/U6 biogenesis, and spliceosome recycling.

The Prp19-associated complex, consisting of at least eight protein components, is involved in spliceosome activation by specifying the interaction of U5 and U6 with pre-mRNA for their stable association with the spliceosome after U4 dissociation. We show here that yeast cells depleted of one or two of the Prp19-associated components, accumulate the free form of U4. In NTC25-deleted cells, the level of U6 was also reduced.

The Prp19-associated complex is required for specifying interactions of U5 and U6 with pre-mRNA during spliceosome activation.

Activation of the spliceosome involves a major structural change in the spliceosome, including release of U1 and U4 small nuclear ribonucleoprotein particles and the addition of a large protein complex, the Prp19-associated complex. We previously showed that the Prp19-associated complex is required for stable association of U5 and U6 with the spliceosome after U4 is released. Changes within the spliceosome upon binding of the Prp19-associated complex include remodeling of the U6/5' splice site interaction and destabilization of Lsm proteins to allow further interaction of U6 with the intron sequence.

The Prp19p-associated complex in spliceosome activation.

During spliceosome activation, a large structural rearrangement occurs that involves the release of two small nuclear RNAs, U1 and U4, and the addition of a protein complex associated with Prp19p. We show here that the Prp19p-associated complex is required for stable association of U5 and U6 with the spliceosome after U4 is dissociated. Ultraviolet crosslinking analysis revealed the existence of two modes of base pairing between U6 and the 5' splice site, as well as a switch of such base pairing from one to the other that required the Prp19p-associated complex during spliceosome activation.