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Differential effect of aneuploidy on the X chromosome and genes with sex-biased expression in Drosophila. Author Affiliations Contributed by James A. Birchler, August 27, 2013 (sent for review July 9, 2013) Significance This study demonstrates a global impact of genomic imbalance on gene expression and the generality of the inverse dosage effect and aneuploid dosage compensation. The study indicates that sex chromosomes and genes with sex-biased expression evolve distinctly in response to dosage-sensitive regulation. Abstract Global analysis of gene expression via RNA sequencing was conducted for trisomics for the left arm of chromosome 2 (2L) and compared with the normal genotype. Footnotes Author contributions: L.S. and J.A.B. designed research; L.S., A.F.J., and A.S.L. performed research; L.S., A.F.J., J.L., J.C., and J.A.B. analyzed data; and L.S. and J.A.B. wrote the paper. Freely available online through the PNAS open access option.

Sign In. Structures of human primase reveal design of nucleotide elongation site and mode of Pol α tethering. Author Affiliations Edited by Mike E. O'Donnell, The Rockefeller University, Howard Hughes Medical Institute, New York, NY, and approved August 21, 2013 (received for review June 12, 2013) Significance DNA synthesis during duplication of the genome depends on primase, the DNA-dependent RNA polymerase that initiates nucleotide polymerization by assembling short RNA primers on the unwound template DNA. The mechanism of DNA priming remains poorly understood, principally because of lack of high-resolution structural information. Our study begins to fill the gap in our knowledge by reporting crystal structures of human primase in unliganded form and bound to UTP.

Abstract Initiation of DNA synthesis in genomic duplication depends on primase, the DNA-dependent RNA polymerase that synthesizes de novo the oligonucleotides that prime DNA replication. Footnotes Freely available online through the PNAS open access option. High-resolution reversible folding of hyperstable RNA tetraloops using molecular dynamics simulations. Author Affiliations Edited by Peter G. Wolynes, Rice University, Houston, TX, and approved August 16, 2013 (received for review May 17, 2013) Significance We report atomistic simulations describing the spontaneous folding of three RNA tetraloops from the unfolded state to within 1–3 Å of their experimentally determined structures.

These common and highly stable motifs serve as building blocks for large structured RNA molecules. Abstract We report the de novo folding of three hyperstable RNA tetraloops to 1–3 Å rmsd from their experimentally determined structures using molecular dynamics simulations initialized in the unfolded state. Footnotes Author contributions: A.A.C. and A.E.G. designed research; A.A.C. performed research; A.A.C. analyzed data; and A.A.C. and A.E.G. wrote the paper. Enhanced group II intron retrohoming in magnesium-deficient Escherichia coli via selection of mutations in the ribozyme core. Key features of σS required for specific recognition by Crl, a transcription factor promoting assembly of RNA polymerase holoenzyme.

Homologous RIG-I–like helicase proteins direct RNAi-mediated antiviral immunity in C. elegans by distinct mechanisms. U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer’s disease. Interrogating translational efficiency and lineage-specific transcriptomes using ribosome affinity purification. Author Affiliations Edited* by J. G. Seidman, Harvard Medical School, Boston, MA, and approved August 7, 2013 (received for review March 10, 2013) Significance We developed reagents and approaches to pull down ribosome-associated RNAs from Cre-labeled cells. We show that this strategy is useful to probe cell type-specific gene expression and the extent of transcript binding to ribosomes. Abstract Transcriptional profiling is a useful strategy to study development and disease. Footnotes Author contributions: P.Z. and W.T.P. designed research; P.Z., Q.M., A.H., B.Z., and S.M.S. performed research; P.Z., J.L., and D.R. contributed new reagents/analytic tools; P.Z., Y.Z., F.G., D.S.D., and W.T.P. analyzed data; and P.Z. and W.T.P. wrote the paper.

Essential ribosome assembly factor Fap7 regulates a hierarchy of RNA–protein interactions during small ribosomal subunit biogenesis. Author Affiliations Edited by James E. Dahlberg, University of Wisconsin Medical School, Madison, WI, and approved August 8, 2013 (received for review April 4, 2013) Significance Ribosomes are complex macromolecular machines universal to all domains of life that synthesize all cellular proteins. They consist of many different protein and RNA building blocks. Abstract Factor activating Pos9 (Fap7) is an essential ribosome biogenesis factor important for the assembly of the small ribosomal subunit with an uncommon dual ATPase and adenylate kinase activity. Footnotes Author contributions: U.A.H., J.P.W., P.K., K. Structures of RNA polymerase II complexes with Bye1, a chromatin-binding PHF3/DIDO homologue.

Author Affiliations Edited by Robert Huber, Max Planck Institute of Biochemistry, Planegg-Martinsried, Germany, and approved August 2, 2013 (received for review June 10, 2013) Significance Transcription of protein-coding genes requires transient binding of many different factors to RNA polymerase II. Thus far, crystal structures of only two such factors in complex with RNA polymerase II are known. Abstract Bypass of Ess1 (Bye1) is a nuclear protein with a domain resembling the central domain in the transcription elongation factor TFIIS.

Footnotes Author contributions: B.D.S. and P.C. designed research; K.K., G.G.W., S.B.R., and M.L. performed research; and K.K. and P.C. wrote the paper. Reconstructing dynamic microRNA-regulated interaction networks. Author Affiliations Edited by Howard Y. Chang, Stanford University, Stanford, CA, and accepted by the Editorial Board July 31, 2013 (received for review February 20, 2013) Abstract The regulation of gene expression in cells, including by microRNAs (miRNAs), is a dynamic process. Current methods for identifying miRNA targets by combining sequence and miRNA and mRNA expression data do not adequately use the temporal information and thus miss important miRNAs and their targets. Footnotes Author contributions: M.H.S., K.V.P., C.L.L.C., N.A., N.K., and Z.B. Tuning a riboswitch response through structural extension of a pseudoknot.

Author Affiliations Edited by David A. Tirrell, California Institute of Technology, Pasadena, CA, and approved July 23, 2013 (received for review March 8, 2013) Significance The three-dimensional fold and inherent structural dynamics of RNA are critical determinants of function. Although the hierarchical folding of RNA secondary structure followed by tertiary structure formation is well established, insights into how secondary structure units impact tertiary structure formation and dynamics remain elusive. Using single-molecule FRET imaging of the preQ1 class II bacterial riboswitch, we reveal that RNA employs stem–loop insertions into classical pseudoknots as a tool to tune ligand response and hence the outcome of natural gene-regulatory elements.

Abstract Structural and dynamic features of RNA folding landscapes represent critical aspects of RNA function in the cell and are particularly central to riboswitch-mediated control of gene expression. Footnotes. Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Differential splicing across immune system lineages.

Composability of regulatory sequences controlling transcription and translation in Escherichia coli. Author Affiliations Edited by Charles R. Cantor, Sequenom, Inc., San Diego, CA, and approved July 2, 2013 (received for review February 11, 2013) Abstract The inability to predict heterologous gene expression levels precisely hinders our ability to engineer biological systems. Using well-characterized regulatory elements offers a potential solution only if such elements behave predictably when combined. We synthesized 12,563 combinations of common promoters and ribosome binding sites and simultaneously measured DNA, RNA, and protein levels from the entire library. Footnotes Author contributions: S.K., D.B.G., and G.M.C. designed research; S.K., D.B.G., and Y.G. performed research; S.K., D.B.G., G.C., V.K.M., A.P.A., and D.E. contributed new reagents/analytic tools; S.K. and D.B.G. analyzed data; and S.K., D.B.G., and G.M.C. wrote the paper.

Reexpression of pyruvate kinase M2 in type 1 myofibers correlates with altered glucose metabolism in myotonic dystrophy. Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration. Author Affiliations Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved July 5, 2013 (received for review May 24, 2013) Abstract Certain lower vertebrates like zebrafish activate proliferation of spared cardiomyocytes after cardiac injury to regenerate lost heart muscle. Here, we used translating ribosome affinity purification to profile translating RNAs in zebrafish cardiomyocytes during heart regeneration.

We identified dynamic induction of several Jak1/Stat3 pathway members following trauma, events accompanied by cytokine production. Footnotes Author contributions: Y.F. and K.D.P. designed research; Y.F., V.G., R.K., and J.E.H. performed research; Y.F., V.G., and K.K. contributed new reagents/analytic tools; Y.F., R.K., and J.E.H. analyzed data; and Y.F. and K.D.P. wrote the paper. Nucleobases bind to and stabilize aggregates of a prebiotic amphiphile, providing a viable mechanism for the emergence of protocells. Author Affiliations Edited* by Steven G. Boxer, Stanford University, Stanford, CA, and approved July 8, 2013 (received for review January 24, 2013) Abstract Primordial cells presumably combined RNAs, which functioned as catalysts and carriers of genetic information, with an encapsulating membrane of aggregated amphiphilic molecules.

Footnotes Author contributions: R.A.B., M.C.B., B.L.S., D.W.D., and S.L.K. designed research; R.A.B., M.C.B., B.L.S., and R.T. performed research; B.L.S. contributed new reagents/analytic tools; R.A.B., M.C.B., B.L.S., R.T., D.W.D., and S.L.K. analyzed data; and R.A.B., M.C.B., B.L.S., and S.L.K. wrote the paper. Metabolic niche of a prominent sulfate-reducing human gut bacterium. Mod5 protein binds to tRNA gene complexes and affects local transcriptional silencing. Author Affiliations Edited* by John Abelson, CalTech, University of California, San Francisco, CA, and approved July 3, 2013 (received for review December 5, 2012) A correction has been published Significance This study provides new insight into the requirements for observed silencing of RNA polymerase II transcription near tRNA genes.

Abstract The tRNA gene-mediated (tgm) silencing of RNA polymerase II promoters is dependent on subnuclear clustering of the tRNA genes, but genetic analysis shows that the silencing requires additional mechanisms. Footnotes Author contributions: M.P. MicroRNA-mediated posttranscriptional regulation is required for maintaining undifferentiated properties of blastoderm and primordial germ cells in chickens. Author Affiliations Edited by George Seidel, Colorado State University, Fort Collins, CO, and approved May 20, 2011 (received for review April 18, 2011) Abstract MicroRNAs (miRNAs) play a critical role in determining the differentiation fate of pluripotent stem cells and germ cells in mammals.

However, the mechanism(s) of miRNA-mediated posttranscriptional regulation with regard to lineage specification and differentiation in chick development require further investigation. Therefore, we conducted miRNA expression profiling to explore specific miRNA signatures in undifferentiated blastoderm and primordial germ cells (PGCs). Footnotes Author contributions: S.I.L., B.R.L., and J.Y.H. designed research; S.I.L., B.R.L., Y.S.H., H.C.L., and D.R. performed research; S.I.L., B.R.L., G.S., T.S.P., and J.Y.H. analyzed data; and S.I.L., B.R.L., D.R., G.S., T.S.P., and J.Y.H. wrote the paper. Fundamental relationship between operon organization and gene expression. Perturbation of thymocyte development in nonsense-mediated decay (NMD)-deficient mice.

Tudor domain containing 7 (Tdrd7) is essential for dynamic ribonucleoprotein (RNP) remodeling of chromatoid bodies during spermatogenesis. Antisense RNA polymerase II divergent transcripts are P-TEFb dependent and substrates for the RNA exosome. Author Affiliations Contributed by Phillip A. Sharp, May 12, 2011 (sent for review March 3, 2011) Abstract Divergent transcription occurs at the majority of RNA polymerase II (RNAPII) promoters in mouse embryonic stem cells (mESCs), and this activity correlates with CpG islands.

Footnotes Author contributions: R.A.F., A.E.A., J.R.Z., and P.A.S. designed research; R.A.F. and A.E.A. performed research; R.A.F., A.E.A., J.R.Z., and P.A.S. analyzed data; and R.A.F., A.E.A., J.R.Z., and P.A.S. wrote the paper. Crystal structure of the MID-PIWI lobe of a eukaryotic Argonaute protein. A riboswitch-regulated antisense RNA in Listeria monocytogenes. Rapid and robust signaling in the CsrA cascade via RNA–protein interactions and feedback regulation. Author Affiliations Edited by Susan Gottesman, National Institutes of Health, Bethesda, MD, and approved June 17, 2013 (received for review May 4, 2013) Abstract Bacterial survival requires the rapid propagation of signals through gene networks during stress, but how this is achieved is not well understood.

This study systematically characterizes the signaling dynamics of a cascade of RNA–protein interactions in the CsrA system, which regulates stress responses and biofilm formation in Escherichia coli. Noncoding RNAs are at the center of the CsrA system; target mRNAs are bound by CsrA proteins that inhibit their translation, CsrA proteins are sequestered by CsrB noncoding RNAs, and the degradation of CsrB RNAs is increased by CsrD proteins. Here, we show using in vivo experiments and quantitative modeling that the CsrA system integrates three strategies to achieve rapid and robust signaling. Footnotes. Experimental and computational analysis of the transition state for ribonuclease A-catalyzed RNA 2′-O-transphosphorylation.

A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus. Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems. Structure of the 70S ribosome bound to release factor 2 and a substrate analog provides insights into catalysis of peptide release. Structure and function of CarD, an essential mycobacterial transcription factor. Isolated pseudo–RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition. Zinc-finger antiviral protein mediates retinoic acid inducible gene I–like receptor-independent antiviral response to murine leukemia virus. Prognostic microRNA/mRNA signature from the integrated analysis of patients with invasive breast cancer. Characterization and comparison of human nuclear and cytosolic editomes. Rotavirus mRNAS are released by transcript-specific channels in the double-layered viral capsid.

Far upstream element-binding protein 1 and RNA secondary structure both mediate second-step splicing repression. RNA splicing regulates the temporal order of TNF-induced gene expression. Anxiety-associated alternative polyadenylation of the serotonin transporter mRNA confers translational regulation by hnRNPK. MiR-9 is an essential oncogenic microRNA specifically overexpressed in mixed lineage leukemia–rearranged leukemia. Modulation of reactivation of latent herpes simplex virus 1 in ganglionic organ cultures by p300/CBP and STAT3. Pyrimidine motif triple helix in the Kluyveromyces lactis telomerase RNA pseudoknot is essential for function in vivo. Conserved microRNA pathway regulates developmental timing of retinal neurogenesis.

Paternally expressed genes predominate in the placenta. Integrated platform for genome-wide screening and construction of high-density genetic interaction maps in mammalian cells. Wolbachia uses a host microRNA to regulate transcripts of a methyltransferase, contributing to dengue virus inhibition in Aedes aegypti. Genome-wide RNAi screen reveals a role for the ESCRT complex in rotavirus cell entry.

Evidence for reactive reduced phosphorus species in the early Archean ocean. Coxsackievirus B3 mutator strains are attenuated in vivo. A microRNA network regulates expression and biosynthesis of wild-type and ΔF508 mutant cystic fibrosis transmembrane conductance regulator. Loss of deeply conserved C-class floral homeotic gene function and C- and E-class protein interaction in a double-flowered ranunculid mutant. Molecular basis of bacterial protein Hen1 activating the ligase activity of bacterial protein Pnkp for RNA repair.

High-amylose wheat generated by RNA interference improves indices of large-bowel health in rats. Admixture and recombination among Toxoplasma gondii lineages explain global genome diversity. Border Cave and the beginning of the Later Stone Age in South Africa. Proceedings of the National Academy of Sciences. C-kit+ precursors support postinfarction myogenesis in the neonatal, but not adult, heart. Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in Drosophila melanogaster. Sign In. CAG expansion induces nucleolar stress in polyglutamine diseases. Early evidence of San material culture represented by organic artifacts from Border Cave, South Africa. Two methods for full-length RNA sequencing for low quantities of cells and single cells.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component. Gyrotropic response in the absence of a bias field. Quantification of the relative roles of niche and neutral processes in structuring gastrointestinal microbiomes. Stress-induced epigenetic regulation of κ-opioid receptor gene involves transcription factor c-Myc. Nascent RNA structure modulates the transcriptional dynamics of RNA polymerases. Nuclear export of single native mRNA molecules observed by light sheet fluorescence microscopy. Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for signaling. Distinct perturbation of the translatome by the antidiabetic drug metformin. INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis.

Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation in the absence of nucleic acids. Fe2+ binds iron responsive element-RNA, selectively changing protein-binding affinities and regulating mRNA repression and activation. Global transcriptome response to ionic liquid by a tropical rain forest soil bacterium, Enterobacter lignolyticus.

Gene regulation via excitation and BDNF is mediated by induction and phosphorylation of the Etv1 transcription factor in cerebellar granule cells. Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis.