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Cell Reports
All content is freely available to readers and supported through open access

Feb 23, 2012

Volume 1Issue 2p83-184
Open Access
On the cover: Localization of mRNA is a prevalent phenomenon observed in various cell types. In this issue, Park et al. present an unbiased analysis method for quantifying intracellular distribution of mRNA. The analytical method is demonstrated with single-molecule FISH and live-cell images revealing the dynamics and function of RNA localization. The cover shows single-molecule FISH images of β-actin mRNA in mouse embryonic fibroblasts. Artwork is by Tatyana A. Harris and is based on images provided by Hye Yoon Park....
On the cover: Localization of mRNA is a prevalent phenomenon observed in various cell types. In this issue, Park et al. present an unbiased analysis method for quantifying intracellular distribution of mRNA. The analytical method is demonstrated with single-molecule FISH and live-cell images revealing the dynamics and function of RNA localization. The cover shows single-molecule FISH images of β-actin mRNA in mouse embryonic fibroblasts. Artwork is by Tatyana A. Harris and is based on images provided by Hye Yoon Park.

Reports

  • Histone H3R2 Symmetric Dimethylation and Histone H3K4 Trimethylation Are Tightly Correlated in Eukaryotic Genomes

    • Chih-Chi Yuan,
    • Adam G.W. Matthews,
    • Yi Jin,
    • Chang Feng Chen,
    • Brad A. Chapman,
    • Toshiro K. Ohsumi,
    • Karen C. Glass,
    • Tatiana G. Kutateladze,
    • Mark L. Borowsky,
    • Kevin Struhl,
    • Marjorie A. Oettinger
    Yuan et al. report the in vivo identification of a histone modification: symmetrical dimethylation of arginine 2 of histone H3 is tightly correlated with H3K4me3 throughout the mouse genome. Mutational analysis in S. cerevisiae reveals that deposition of H3R2me2s requires the same Set1 complex that deposits H3K4me3. Yuan et al.'s work suggests that H3R2me2sK4me3, not simply H3K4me3 alone, is the mark of active promoters and that factors that recognize H3K4me3 will have their binding modulated by their preference for H3R2me2s.
  • Long Telomeres Bypass the Requirement for Telomere Maintenance in Human Tumorigenesis

    • Michael A.S. Taboski,
    • David C.F. Sealey,
    • Jennifer Dorrens,
    • Chandrakant Tayade,
    • Dean H. Betts,
    • Lea Harrington
    Human tumor cells were engineered with long telomeres and genetically excisable telomerase reverse transcriptase (TERT). Upon TERT removal, tumor formation in vitro and in a xenograft murine model was robust despite the absence of telomere maintenance. The eventual loss of telomeric signal and onset of cell death was not accompanied by induction of endogenous telomerase or other telomere maintenance mechanisms, lending support to the notion that telomerase inhibition may be a tractable therapy even in tumors with initially long telomeres.
  • Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency

    • Fella Hammachi,
    • Gillian M. Morrison,
    • Alexei A. Sharov,
    • Alessandra Livigni,
    • Santosh Narayan,
    • Eirini P. Papapetrou,
    • James O'Malley,
    • Keisuke Kaji,
    • Minoru S.H. Ko,
    • Mark Ptashne,
    • Joshua M. Brickman
    Oct4 is a key transcription factor involved in both the maintenance of embryonic stem cells (ESCs) and the reprogramming of somatic cells to an ESC-like pluripotent state (induced pluripotent stem cells; iPSCs). How does Oct4 support and induce these states? Here, Brickman and colleagues show that activation of a network of gene expression by Oct4 is sufficient to both maintain and reprogram pluripotent cell states.
  • Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC

    • Shipra Das,
    • Olga Anczuków,
    • Martin Akerman,
    • Adrian R. Krainer
    The SR protein splicing factor SRSF1 is a potent proto-oncogene that is frequently upregulated in cancer. Das and colleagues show that SRSF1 expression is regulated by the transcription factor oncoprotein MYC. MYC directly activates transcription of SRSF1, and through it MYC alters the cellular alternative splicing profile. Furthermore, the increase in SRSF1 protein level contributes to MYC-mediated transformation. The present study thus identifies a critical functional target of MYC and demonstrates the key role of alternative splicing in oncogenesis.

Articles

  • Frequent Recent Origination of Brain Genes Shaped the Evolution of Foraging Behavior in Drosophila

    • Sidi Chen,
    • Maria Spletter,
    • Xiaochun Ni,
    • Kevin P. White,
    • Liqun Luo,
    • Manyuan Long
    The evolution of genetic components in the brain is coupled with the evolution of animal behavior. Long and colleagues show that new genes have frequently arisen in the Drosophila genome under natural selection. These young genes are expressed in the brain and enriched in the mushroom bodies, which are important for olfaction. Loss of the young gene Xcbp1 or Desr leads to defects in foraging behavior, illustrating how newly evolved genes influenced the genetic system of behavior in D. melanogaster.
  • Optimization of Gene Expression through Divergent Mutational Paths

    • Hsin-Hung Chou,
    • Christopher J. Marx
    Phenotypic parallelism is often observed for evolution under similar selection, but to what extent do similar underlying genotypic changes account for this? We examined the genotypic and phenotypic evolution of replicate populations founded by an engineered bacterium expressing an essential but costly metabolic pathway. To balance its cost and benefit, all populations evolved reduced expression of pathway genes toward an intermediate optimum. This phenotypic repeatability, however, involved diverse mutational events that employed at least three distinct molecular mechanisms to alter gene expression.
  • miR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages

    • Mario Leonardo Squadrito,
    • Ferdinando Pucci,
    • Laura Magri,
    • Davide Moi,
    • Gregor D. Gilfillan,
    • Anna Ranghetti,
    • Andrea Casazza,
    • Massimiliano Mazzone,
    • Robert Lyle,
    • Luigi Naldini,
    • Michele De Palma
    The mannose receptor (MRC1) is an endocytic receptor highly expressed by proangiogenic and protumoral macrophages. Squadrito and colleagues characterize the bioactivity and function of miR-511-3p, an intronic microRNA encoded by the Mrc1 gene. They show that transcriptional upregulation of Mrc1 in protumoral macrophages induces a genetic program regulated by miR-511-3p, which limits rather than enhances their protumoral functions. These findings reveal an unexpected role for MRC1 as negative regulator of the protumoral genetic programs of macrophages.
  • The Mechanisms of Repetitive Spike Generation in an Axonless Retinal Interneuron

    • Mark S. Cembrowski,
    • Stephen M. Logan,
    • Miao Tian,
    • Li Jia,
    • Wei Li,
    • William L. Kath,
    • Hermann Riecke,
    • Joshua H. Singer
    The AII amacrine cell is a retinal interneuron that lacks an axon but exhibits small somatic spikes. Cembrowski and colleagues find that these spikes represent electrically filtered action potential-like events that arise in a single, electrotonically isolated dendritic process. They conclude that the axonless AII possesses a cellular compartment that bears a striking resemblance to the axon initial segment of more traditional neurons, yet spikes initiated at this site are attenuated across the vast majority of the AII membrane.

Resources

  • Integrative Genome-wide Analysis Reveals Cooperative Regulation of Alternative Splicing by hnRNP Proteins

    • Stephanie C. Huelga,
    • Anthony Q. Vu,
    • Justin D. Arnold,
    • Tiffany Y. Liang,
    • Patrick P. Liu,
    • Bernice Y. Yan,
    • John Paul Donohue,
    • Lily Shiue,
    • Shawn Hoon,
    • Sydney Brenner,
    • Manuel Ares Jr.,
    • Gene W. Yeo
    Heterogeneous nuclear ribonucleoparticle (hnRNP) proteins are among the most abundant RNA binding proteins (RBPs) and regulate cellular RNA levels. Through the integration of several genomic approaches, Huelga, Yeo, and colleagues have identified thousands of binding sites, splicing events, and regulated genes for major hnRNP proteins A1, A2/B1, F, H1, M, and U. HnRNP proteins cross- and autoregulate each other and a whole network of RBPs. These findings define an unprecedented degree of complexity and compensatory relationships among hnRNP proteins.
  • An Unbiased Analysis Method to Quantify mRNA Localization Reveals Its Correlation with Cell Motility

    • Hye Yoon Park,
    • Tatjana Trcek,
    • Amber L. Wells,
    • Jeffrey A. Chao,
    • Robert H. Singer
    Localization of mRNA has been mostly analyzed by qualitative descriptions. Park et al. now report an unbiased analysis method to quantify intracellular localization using polarization and dispersion indices of mRNA distribution. The method is demonstrated using single molecule FISH images of budding yeast and chicken embryonic fibroblasts. Live-cell analysis of β-actin mRNA distribution reveals the life-time of the localization pattern and its correlation with cell motility.
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