Hyeshik Chang

Nature Structural & Molecular Biology 20, 936 (2013). doi:10.1038/nsmb.2635

Authors: David Zünd, Andreas R Gruber, Mihaela Zavolan & Oliver Mühlemann

Analysis: Don't do big-data science backwards

Nature 499, 7458 (2013). doi:10.1038/499284d

Authors: David B. Lindenmayer & Gene E. Likens

Large open-access data sets offer unprecedented opportunities for scientific discovery — the current global collapse of bee and frog populations are classic examples. However, we must resist the temptation to do science backwards by posing questions after, rather than before, data analysis.A scant understanding

Article

The complexity and dynamic range of mammalian proteomes has stymied comprehensive protein quantification for the past twenty years. Zhou et al . develop DEEP SEQ mass spectrometry and use it to quantify a murine stem cell proteome to a depth equivalent to RNA-seq-based ribosome profiling.

Nature Communications doi: 10.1038/ncomms3171

Authors: Feng Zhou, Yu Lu, Scott B. Ficarro, Guillaume Adelmant, Wenyu Jiang, C. John Luckey, Jarrod A. Marto

Nature Protocols 8, 1551 (2013). doi:10.1038/nprot.2013.092

Authors: Huaiyu Mi, Anushya Muruganujan, John T Casagrande & Paul D Thomas

The PANTHER (protein annotation through evolutionary relationship) classification system (http://www.pantherdb.org/) is a comprehensive system that combines gene function, ontology, pathways and statistical analysis tools that enable biologists to analyze large-scale, genome-wide data from sequencing, proteomics or gene expression experiments. The system is built

Jacqueline K. White, Anna-Karin Gerdin, Natasha A. Karp, Ed Ryder, Marija Buljan, James N. Bussell, Jennifer Salisbury, Simon Clare, Neil J. Ingham, Christine Podrini, Richard Houghton, Jeanne Estabel, Joanna R. Bottomley, David G. Melvin, David Sunter, Niels C. Adams, David Tannahill, Darren W. Logan, Daniel G. MacArthur, Jonathan Flint, Vinit B. Mahajan, Stephen H. Tsang, Ian Smyth, Fiona M. Watt, William C. Skarnes, Gordon Dougan, David J. Adams, Ramiro Ramirez-Solis, Allan Bradley, Karen P. Steel. Mutations in whole organisms are powerful ways of interrogating gene function in a realistic context. We describe a program, the Sanger Institute Mouse Genetics Project, that provides a step towar....

A proof-of-principle study reports somatic reprogramming to the pluripotent state using small-molecule compounds.

Authors: Pingping Hou, Yanqin Li, Xu Zhang, Chun Liu, Jingyang Guan, Honggang Li, Ting Zhao, Junqing Ye, Weifeng Yang, Kang Liu, Jian Ge, Jun Xu, Qiang Zhang, Yang Zhao, Hongkui Deng

Eukaryotes can have thousands of 45S ribosomal RNA (rRNA) genes, many of which are silenced during development. Using fluorescence-activated sorting techniques, we show that active rRNA genes in Arabidopsis thaliana are present within sorted nucleoli, whereas silenced rRNA genes are excluded. DNA methyltransferase (met1), histone deacetylase (hda6), or chromatin assembly (caf1) mutants that disrupt silencing abrogate this nucleoplasmic–nucleolar partitioning. Bisulfite sequencing data indicate that active nucleolar rRNA genes are nearly completely demethylated at promoter CGs, whereas silenced genes are nearly fully methylated. Collectively, the data reveal that rRNA genes occupy distinct but changeable nuclear territories according to their epigenetic state.

When adapting to environmental stress, cells attenuate and reprogram their translational output. In part, these altered translation profiles are established through changes in the interactions between RNA-binding proteins and mRNAs. The Argonaute 2 (Ago2)/microRNA (miRNA) machinery has been shown to participate in stress-induced translational up-regulation of a particular mRNA, CAT-1; however, a detailed, transcriptome-wide understanding of the involvement of Ago2 in the process has been lacking. Here, we profiled the overall changes in Ago2–mRNA interactions upon arsenite stress by cross-linking immunoprecipitation (CLIP) followed by high-throughput sequencing (CLIP-seq). Ago2 displayed a significant remodeling of its transcript occupancy, with the majority of 3' untranslated region (UTR) and coding sequence (CDS) sites exhibiting stronger interaction. Interestingly, target sites that were destined for release from Ago2 upon stress were depleted in miRNA complementarity signatures, suggesting an alternative mode of interaction. To compare the changes in Ago2-binding patterns across transcripts with changes in their translational states, we measured mRNA profiles on ribosome/polysome gradients by RNA sequencing (RNA-seq). Increased Ago2 occupancy correlated with stronger repression of translation for those mRNAs, as evidenced by a shift toward lighter gradient fractions upon stress, while release of Ago2 was associated with the limited number of transcripts that remained translated. Taken together, these data point to a role for Ago2 and the mammalian miRNAs in mediating the translational component of the stress response.

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Multiple products from microRNA transcripts.

Biochem Soc Trans. 2013 Aug 1;41(4):850-4

Authors: Marco A, Ninova M, Griffiths-Jones S

Abstract
A single transcript sometimes codes for more than one product. In bacteria, and in a few exceptional animal lineages, many genes are organized into operons: clusters of open reading frames that are transcribed together in a single polycistronic transcript. However, polycistronic transcripts are rare in eukaryotes. One notable exception is that of miRNAs (microRNAs), small RNAs that regulate gene expression at the post-transcriptional level. The primary transcripts of miRNAs commonly produce more than one functional product, by at least three different mechanisms. miRNAs are often produced from polycistronic transcripts together with other miRNA precursors. Also, miRNAs frequently derive from protein-coding gene introns. Finally, each miRNA precursor can produce two mature miRNA products. We argue, in the present review, that miRNAs are frequently hosted in transcripts coding for multiple products because new miRNA precursor sequences that arise by chance in transcribed regions are more likely to become functional miRNAs during evolution.

PMID: 23863143 [PubMed - in process]

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Cellular functions of the microprocessor.

Biochem Soc Trans. 2013 Aug 1;41(4):838-43

Authors: Macias S, Cordiner RA, Cáceres JF

Abstract
The microprocessor is a complex comprising the RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 (DiGeorge syndrome critical region 8 gene) that catalyses the nuclear step of miRNA (microRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as an endonuclease. Recent global analyses of microprocessor and Dicer proteins have suggested novel functions for these components independent of their role in miRNA biogenesis. A HITS-CLIP (high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation) experiment designed to identify novel substrates of the microprocessor revealed that this complex binds and regulates a large variety of cellular RNAs. The microprocessor-mediated cleavage of several classes of RNAs not only regulates transcript levels, but also modulates alternative splicing events, independently of miRNA function. Importantly, DGCR8 can also associate with other nucleases, suggesting the existence of alternative DGCR8 complexes that may regulate the fate of a subset of cellular RNAs. The aim of the present review is to provide an overview of the diverse functional roles of the microprocessor.

PMID: 23863141 [PubMed - in process]

by Marco Pautasso

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Transfection of siRNAs can alter miRNA levels and trigger non-specific protein degradation in mammalian cells.

Biochim Biophys Acta. 2013 May;1829(5):455-68

Authors: Liang XH, Hart CE, Crooke ST

Abstract
Sequence-non-specific effects of siRNAs that alter the expression of non-targeted genes have been reported, including competition of siRNAs with endogenous RISC components. However, the detailed mechanisms and subsequent effects of such competition are not well documented. Here we analyze the competition of miRNAs in mammalian cells with low concentrations of siRNAs, and found that: 1) transfection of different siRNAs in the low nanomolar range used to deplete target RNAs can reduce the levels of miRNAs in different cell types, 2) siRNA transfection results in rapid reduction of Ago2-associated miRNAs concurrent with accumulation of Ago2-bound siRNAs and a significant change in the expression levels of many miRNAs, 3) competition largely depends on Ago2 and not Dicer, 4) microarray analysis showed that the majority of highly expressed miRNAs are reduced, in a siRNA concentration dependent manner, and low abundant miRNAs may be unchanged or repressed and a few miRNAs appear to have increased levels, and 5) consistent with previous studies, the expression levels of mRNAs that are targeted by highly repressed miRNAs are preferentially increased. As a consequence of such competition, we observed that α-tubulin, a substrate of two up-regulated proteases, granzyme B and granzyme M, was rapidly degraded at the protein level upon siRNA transfection. Our results support a model in which transfection of siRNAs can change the levels of many miRNAs by competition for Ago2, leading to altered expression of many miRNA target genes, which can in turn affect downstream gene expression even at the protein level.

PMID: 23403288 [PubMed - indexed for MEDLINE]

Heterogeneous nuclear ribonucleoprotein (hnRNP) K genome wide binding survey reveals its role in regulating 3' end RNA processing and transcription termination at early growth response 1 (EGR1) gene through XRN2 exonuclease.

J Biol Chem. 2013 Jul 15;

Authors: Mikula M, Bomsztyk K, Goryca K, Chojnowski K, Ostrowski J

Abstract
The heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a nucleic acid-binding protein that acts as a docking platform integrating signal transduction pathways to nucleic acid-related processes. Given that hnRNPK could be involved in other steps that compose gene expression the definition of its genome wide occupancy is important to better understand its role in transcription and co-transcriptional processes. Here, we used chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) to analyze genome-wide hnRNPK-DNA interaction in colon cancer cell line HCT116. 9.1/3.6 and 7.0/3.4 million tags were sequenced/mapped then 1809 and 642 hnRNPK binding sites were detected in quiescent and 30 minutes serum stimulated cells, respectively. The inspection of sequencing tracks revealed inducible hnRNPK recruitment along a number of immediate early gene loci, including EGR1 and ZFP36, with highest densities present at the transcription termination sites. Strikingly, hnRNPK knockdown with siRNA resulted in increased pre-RNA levels transcribed downstream of the EGR1 poly-adenylation (A) site suggesting altered 3' end pre-RNA degradation. Further ChIP survey of hnRNPK knockdown uncovered decreased recruitment of the 5' - 3' exonuclease XRN2 along EGR1 and downstream of the poly-(A) signal without altering RNA Polymerase II density at these sites. Immunoprecipitation of hnRNPK and XRN2 from intact and RNase A treated nuclear extracts followed by shotgun mass spectrometry revealed hnRNPK and XRN2 presence in the same complexes along with other spliceosome-related proteins. Our data suggest that hnRNPK may play a role in recruitment of XRN2 to gene loci thus regulating coupling 3' end pre-mRNA processing to transcription termination.

PMID: 23857582 [PubMed - as supplied by publisher]

Triplex is emerging as an important RNA tertiary structure motif, in which consecutive non-canonical base pairs form between a duplex and a third strand. RNA duplex region is also often functionally important site for protein binding. Thus, triplex-forming oligonucleotides (TFOs) may be developed to regulate various biological functions involving RNA, such as viral ribosomal frameshifting and reverse transcription. How chemical modification in TFOs affects RNA triplex stability, however, is not well understood. Here, we incorporated locked nucleic acid, 2-thio U- and 2'-O methyl-modified residues in a series of all pyrimidine RNA TFOs, and we studied the binding to two RNA hairpin structures. The 12-base-triple major-groove pyrimidine–purine–pyrimidine triplex structures form between the duplex regions of RNA/DNA hairpins and the complementary RNA TFOs. Ultraviolet-absorbance-detected thermal melting studies reveal that the locked nucleic acid and 2-thio U modifications in TFOs strongly enhance triplex formation with both parental RNA and DNA duplex regions. In addition, we found that incorporation of 2'-O methyl-modified residues in a TFO destabilizes and stabilizes triplex formation with RNA and DNA duplex regions, respectively. The (de)stabilization of RNA triplex formation may be facilitated through modulation of van der Waals contact, base stacking, hydrogen bonding, backbone pre-organization, geometric compatibility and/or dehydration energy. Better understanding of the molecular determinants of RNA triplex structure stability lays the foundation for designing and discovering novel sequence-specific duplex-binding ligands as diagnostic and therapeutic agents targeting RNA.

CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes.

Cell. 2013 Jul 9;

Authors: Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE, Stern-Ginossar N, Brandman O, Whitehead EH, Doudna JA, Lim WA, Weissman JS, Qi LS

Abstract
The genetic interrogation and reprogramming of cells requires methods for robust and precise targeting of genes for expression or repression. The CRISPR-associated catalytically inactive dCas9 protein offers a general platform for RNA-guided DNA targeting. Here, we show that fusion of dCas9 to effector domains with distinct regulatory functions enables stable and efficient transcriptional repression or activation in human and yeast cells, with the site of delivery determined solely by a coexpressed short guide (sg)RNA. Coupling of dCas9 to a transcriptional repressor domain can robustly silence expression of multiple endogenous genes. RNA-seq analysis indicates that CRISPR interference (CRISPRi)-mediated transcriptional repression is highly specific. Our results establish that the CRISPR system can be used as a modular and flexible DNA-binding platform for the recruitment of proteins to a target DNA sequence, revealing the potential of CRISPRi as a general tool for the precise regulation of gene expression in eukaryotic cells.

PMID: 23849981 [PubMed - as supplied by publisher]

In vivo mapping of RNA-RNA interactions in Staphylococcus aureus using the endoribonuclease III.

Methods. 2013 Jul 9;

Authors: Lioliou E, Sharma CM, Altuvia Y, Caldelari I, Romilly C, Helfer AC, Margalit H, Romby P

Abstract
Ribonucleases play key roles in gene regulation and in the expression of virulence factors in Staphylococcus aureus. Among these enzymes, the double-strand specific endoribonucleaseIII (RNase III) is a key mediator of mRNA processing and degradation. Recently, we have defined, direct target sites for RNase III processing on a genome-wide scale in S. aureus. Our approach is based on deep sequencing of cDNA libraries obtained from RNAs isolated by in vivo co-immunoprecipitation with wild-type RNase III and two cleavage-defective mutants. The use of such catalytically inactivated enzymes, which still retain their RNA binding capacity, allows the identification of novel RNA substrates of RNaseIII. In this report, we will summarize the diversity of RNase III functions, discuss the advantages and the limitations of the approach, and how this strategy identifies novel mRNA targets of small non-coding RNAs in S. aureus.

PMID: 23851283 [PubMed - as supplied by publisher]

lncRNome: a comprehensive knowledgebase of human long noncoding RNAs.

Database (Oxford). 2013;2013(0):bat034

Authors: Bhartiya D, Pal K, Ghosh S, Kapoor S, Jalali S, Panwar B, Jain S, Sati S, Sengupta S, Sachidanandan C, Raghava GP, Sivasubbu S, Scaria V

Abstract
The advent of high-throughput genome scale technologies has enabled us to unravel a large amount of the previously unknown transcriptionally active regions of the genome. Recent genome-wide studies have provided annotations of a large repertoire of various classes of noncoding transcripts. Long noncoding RNAs (lncRNAs) form a major proportion of these novel annotated noncoding transcripts, and presently known to be involved in a number of functionally distinct biological processes. Over 18 000 transcripts are presently annotated as lncRNA, and encompass previously annotated classes of noncoding transcripts including large intergenic noncoding RNA, antisense RNA and processed pseudogenes. There is a significant gap in the resources providing a stable annotation, cross-referencing and biologically relevant information. lncRNome has been envisioned with the aim of filling this gap by integrating annotations on a wide variety of biologically significant information into a comprehensive knowledgebase. To the best of our knowledge, lncRNome is one of the largest and most comprehensive resources for lncRNAs. Database URL: http://genome.igib.res.in/lncRNome.

PMID: 23846593 [PubMed - as supplied by publisher]

Widespread purifying selection on RNA structure in mammals.

Nucleic Acids Res. 2013 Jul 11;

Authors: Smith MA, Gesell T, Stadler PF, Mattick JS

Abstract
Evolutionarily conserved RNA secondary structures are a robust indicator of purifying selection and, consequently, molecular function. Evaluating their genome-wide occurrence through comparative genomics has consistently been plagued by high false-positive rates and divergent predictions. We present a novel benchmarking pipeline aimed at calibrating the precision of genome-wide scans for consensus RNA structure prediction. The benchmarking data obtained from two refined structure prediction algorithms, RNAz and SISSIz, were then analyzed to fine-tune the parameters of an optimized workflow for genomic sliding window screens. When applied to consistency-based multiple genome alignments of 35 mammals, our approach confidently identifies >4 million evolutionarily constrained RNA structures using a conservative sensitivity threshold that entails historically low false discovery rates for such analyses (5-22%). These predictions comprise 13.6% of the human genome, 88% of which fall outside any known sequence-constrained element, suggesting that a large proportion of the mammalian genome is functional. As an example, our findings identify both known and novel conserved RNA structure motifs in the long noncoding RNA MALAT1. This study provides an extensive set of functional transcriptomic annotations that will assist researchers in uncovering the precise mechanisms underlying the developmental ontologies of higher eukaryotes.

PMID: 23847102 [PubMed - as supplied by publisher]

by Chao Cheng, Matthew Ung, Gavin D. Grant, Michael L. Whitfield

Cell cycle is a complex and highly supervised process that must proceed with regulatory precision to achieve successful cellular division. Despite the wide application, microarray time course experiments have several limitations in identifying cell cycle genes. We thus propose a computational model to predict human cell cycle genes based on transcription factor (TF) binding and regulatory motif information in their promoters. We utilize ENCODE ChIP-seq data and motif information as predictors to discriminate cell cycle against non-cell cycle genes. Our results show that both the trans- TF features and the cis- motif features are predictive of cell cycle genes, and a combination of the two types of features can further improve prediction accuracy. We apply our model to a complete list of GENCODE promoters to predict novel cell cycle driving promoters for both protein-coding genes and non-coding RNAs such as lincRNAs. We find that a similar percentage of lincRNAs are cell cycle regulated as protein-coding genes, suggesting the importance of non-coding RNAs in cell cycle division. The model we propose here provides not only a practical tool for identifying novel cell cycle genes with high accuracy, but also new insights on cell cycle regulation by TFs and cis-regulatory elements.

by Hadas Zur, Tamir Tuller

The accepted model of eukaryotic translation initiation begins with the scanning of the transcript by the pre-initiation complex from the 5′end until an ATG codon with a specific nucleotide (nt) context surrounding it is recognized (Kozak rule). According to this model, ATG codons upstream to the beginning of the ORF should affect translation. We perform for the first time, a genome-wide statistical analysis, uncovering a new, more comprehensive and quantitative, set of initiation rules for improving the cost of translation and its efficiency. Analyzing dozens of eukaryotic genomes, we find that in all frames there is a universal trend of selection for low numbers of ATG codons; specifically, 16–27 codons upstream, but also 5–11 codons downstream of the START ATG, include less ATG codons than expected. We further suggest that there is selection for anti optimal ATG contexts in the vicinity of the START ATG. Thus, the efficiency and fidelity of translation initiation is encoded in the 5′UTR as required by the scanning model, but also at the beginning of the ORF. The observed nt patterns suggest that in all the analyzed organisms the pre-initiation complex often misses the START ATG of the ORF, and may start translation from an alternative initiation start-site. Thus, to prevent the translation of undesired proteins, there is selection for nucleotide sequences with low affinity to the pre-initiation complex near the beginning of the ORF. With the new suggested rules we were able to obtain a twice higher correlation with ribosomal density and protein levels in comparison to the Kozak rule alone (e.g. for protein levels r = 0.7 vs. r = 0.31; p−12).

Five European individuals who lived during the Middle Ages provide a look backward at leprosy.

Authors: Verena J. Schuenemann, Pushpendra Singh, Thomas A. Mendum, Ben Krause-Kyora, Günter Jäger, Kirsten I. Bos, Alexander Herbig, Christos Economou, Andrej Benjak, Philippe Busso, Almut Nebel, Jesper L. Boldsen, Anna Kjellström, Huihai Wu, Graham R. Stewart, G. Michael Taylor, Peter Bauer, Oona Y.-C. Lee, Houdini H.T. Wu, David E. Minnikin, Gurdyal S. Besra, Katie Tucker, Simon Roffey, Samba O. Sow, Stewart T. Cole, Kay Nieselt, Johannes Krause

A compendium of RNA-binding motifs for decoding gene regulation

Nature 499, 7457 (2013). doi:10.1038/nature12311

Authors: Debashish Ray, Hilal Kazan, Kate B. Cook, Matthew T. Weirauch, Hamed S. Najafabadi, Xiao Li, Serge Gueroussov, Mihai Albu, Hong Zheng, Ally Yang, Hong Na, Manuel Irimia, Leah H. Matzat, Ryan K. Dale, Sarah A. Smith, Christopher A. Yarosh, Seth M. Kelly, Behnam Nabet, Desirea Mecenas, Weimin Li, Rakesh S. Laishram, Mei Qiao, Howard D. Lipshitz, Fabio Piano, Anita H. Corbett, Russ P. Carstens, Brendan J. Frey, Richard A. Anderson, Kristen W. Lynch, Luiz O. F. Penalva, Elissa P. Lei, Andrew G. Fraser, Benjamin J. Blencowe, Quaid D. Morris & Timothy R. Hughes

RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins

Nature Biotechnology 31, 577 (2013). doi:10.1038/nbt0713-577

Author: Aaron Bouchie

Background: Transcriptome sequencing and assembly represent a great resource for the study of non-model species,and many metrics have been used to evaluate and compare these assemblies. Unfortunately, it is stillunclear which of these metrics accurately reflect assembly quality. Results: We simulated sequencing transcripts of Drosophila melanogaster. By assembling these simulatedreads using both a "perfect" and a modern transcriptome assembler while varying read lengthand sequencing depth, we evaluated quality metrics to determine whether they 1) revealed perfectassemblies to be of higher quality, and 2) revealed perfect assemblies to be more complete as dataquantity increased.Several commonly used metrics were not consistent with these expectations, including averagecontig coverage and length, though they became consistent when singletons were included in theanalysis. We found several annotation-based metrics to be consistent and informative, including contigreciprocal best hit count and contig unique annotation count. Finally, we evaluated a number of novelmetrics such as reverse annotation count, contig collapse factor, and the ortholog hit ratio, discoveringthat each assess assembly quality in unique ways. Conclusions: Although much attention has been given to transcriptome assembly, little research has focused ondetermining how best to evaluate assemblies, particularly in light of the variety of options availablefor read length and sequencing depth. Our results provide an important review of these metrics andgive researchers tools to produce the highest quality transcriptome assemblies.

Nature Reviews Genetics. doi:10.1038/nrg3534

Author: Louisa Flintoft

The EMBO Journal. doi:10.1038/emboj.2013.155

Authors: Yi Shao, Lihui Feng, Steven T Rutherford, Kai Papenfort & Bonnie L Bassler

Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3' UTRs.

Nat Struct Mol Biol. 2013 Jul 7;

Authors: Zünd D, Gruber AR, Zavolan M, Mühlemann O

Abstract
Recruitment of the UPF1 nonsense-mediated mRNA decay (NMD) factor to target mRNAs was initially proposed to occur through interaction with release factors at terminating ribosomes. However, recently emerging evidence points toward translation-independent interaction with the 3' untranslated region (UTR) of mRNAs. We mapped transcriptome-wide UPF1-binding sites by individual-nucleotide-resolution UV cross-linking and immunoprecipitation in human cells and found that UPF1 preferentially associated with 3' UTRs in translationally active cells but underwent significant redistribution toward coding regions (CDS) upon translation inhibition, thus indicating that UPF1 binds RNA before translation and gets displaced from the CDS by translating ribosomes. Corroborated by RNA immunoprecipitation and by UPF1 cross-linking to long noncoding RNAs, our evidence for translation-independent UPF1-RNA interaction suggests that the triggering of NMD occurs after UPF1 binding to mRNA, presumably through activation of RNA-bound UPF1 by aberrant translation termination.

PMID: 23832275 [PubMed - as supplied by publisher]

Biology must develop its own big-data systems

Nature 499, 7456 (2013). http://www.nature.com/doifinder/10.1038/499007a

Author: John Boyle

Too many data-management projects fail because they ignore the changing nature of life-sciences data, argues John Boyle.

lincRNAs: Genomics, Evolution, and Mechanisms.

Cell. 2013 Jul 3;154(1):26-46

Authors: Ulitsky I, Bartel DP

Abstract
Long intervening noncoding RNAs (lincRNAs) are transcribed from thousands of loci in mammalian genomes and might play widespread roles in gene regulation and other cellular processes. This Review outlines the emerging understanding of lincRNAs in vertebrate animals, with emphases on how they are being identified and current conclusions and questions regarding their genomics, evolution and mechanisms of action.

PMID: 23827673 [PubMed - in process]

DHX34 and NBAS form part of an autoregulatory NMD circuit that regulates endogenous RNA targets in human cells, zebrafish and Caenorhabditis elegans.

Nucleic Acids Res. 2013 Jul 4;

Authors: Longman D, Hug N, Keith M, Anastasaki C, Patton EE, Grimes G, Cáceres JF

Abstract
The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons but also regulates the abundance of cellular RNAs. We sought to identify transcripts that are regulated by two novel NMD factors, DHX34 and neuroblastoma amplified sequence (NBAS), which were identified in a genome-wide RNA interference screen in Caenorhabditis elegans and later shown to mediate NMD in vertebrates. We performed microarray expression profile analysis in human cells, zebrafish embryos and C. elegans that were individually depleted of these factors. Our analysis revealed that a significant proportion of genes are co-regulated by DHX34, NBAS and core NMD factors in these three organisms. Further analysis indicates that NMD modulates cellular stress response pathways and membrane trafficking across species. Interestingly, transcripts encoding different NMD factors were sensitive to DHX34 and NBAS depletion, suggesting that these factors participate in a conserved NMD negative feedback regulatory loop, as was recently described for core NMD factors. In summary, we find that DHX34 and NBAS act in concert with core NMD factors to co-regulate a large number of endogenous RNA targets. Furthermore, the conservation of a mechanism to tightly control NMD homeostasis across different species highlights the importance of the NMD response in the control of gene expression.

PMID: 23828042 [PubMed - as supplied by publisher]