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Rethinking gene regulatory networks in light of alternative splicing, intrinsically disordered protein domains, and post-translational modifications

Karl J. Niklas, Sarah E. Bondos, A. Keith Dunker, Stuart A. Newman
2015 Frontiers in Cell and Developmental Biology  
Mounting evidence shows, however, that most eukaryotic precursor RNAs undergo alternative splicing (AS) and that the majority of transcription factors contain intrinsically disordered protein (IDP) domains  ...  Models for genetic regulation and cell fate specification characteristically assume that gene regulatory networks (GRNs) are essentially deterministic and exhibit multiple stable states specifying alternative  ...  Funding from the College of Agriculture and Life Sciences, Cornell University (to K. J. N.) and from NSF CAREER 1151394 and the Ted Nash Long Life Foundation M1500779 (to S. E.  ... 
doi:10.3389/fcell.2015.00008 pmid:25767796 pmcid:PMC4341551 fatcat:7dalfwjjdjgpvg23fzwh5tyvo4

Convergent Evolution of Fern-Specific Mitochondrial Group II Intron atp1i361g2 and Its Ancient Source Paralogue rps3i249g2 and Independent Losses of Intron and RNA Editing among Pteridaceae

Simon Maria Zumkeller, Volker Knoop, Nils Knie
2016 Genome Biology and Evolution  
Instead, we now observe that RNA editing events in both directions of pyrimidine exchange (C-to-U and U-to-C) are retained in atp1 exons after loss of the intron in Pteris argyraea/biaurita and in Actiniopteris  ...  We conclude that atp1i361g2 may have originated from the more ancestral rps3i249g2 paralogue by a reverse splicing copy event early in the evolution of monilophytes.  ...  In particular, we wish to thank the curator of the Bonn Botanic Garden, Dr Wolfram Lobin, and his team, especially Mr Bernd Reinken, for support and expert consultation.  ... 
doi:10.1093/gbe/evw173 pmid:27492234 pmcid:PMC5010907 fatcat:zjp376rtmjg4bd3rsxdsyitlku

An intriguing RNA species—perspectives of circularized RNA

Ting Shen, Miao Han, Gang Wei, Ting Ni
2015 Protein & Cell  
Circular RNAs (circRNAs), a kind of covalently closed RNA molecule, were used to be considered a type of byproducts of mis-splicing events and were discovered sporadically due to the technological limits  ...  in the early years.  ...  Similar to the idea that RBPs can regulate alternative splicing and alternative polyadenylation, the local concentration of RBPs also holds the potential to affect the alternative circularization in circRNA  ... 
doi:10.1007/s13238-015-0202-0 pmid:26349458 pmcid:PMC4656206 fatcat:npo2ph2rdvgh5gao3p3lmnofuu

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins

Vladimir N. Uversky
2016 Journal of Biological Chemistry  
Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional  ...  , and can be considered an important part of the structure-function continuum.  ...  Acknowledgment-I am thankful to Alexey Uversky for careful reading and editing this manuscript.  ... 
doi:10.1074/jbc.r115.685859 pmid:26851286 pmcid:PMC4807255 fatcat:5e4xvdfxvvf2hg5ld7e3ybigji

Chaos and Hyperchaos in a Model of Ribosome Autocatalytic Synthesis

Vitaly A. Likhoshvai, Vladislav V. Kogai, Stanislav I. Fadeev, Tamara M. Khlebodarova
2016 Scientific Reports  
The biological interpretation of the modeling results and parameter estimation suggest the feasibility of chaotic dynamics in molecular genetic systems of eukaryotes, which depends only on the internal  ...  In current work we present an elementary model in which the autocatalytic synthesis of ribosomal RNA and proteins, as well as enzymes ensuring their degradation are described with two monotonically increasing  ...  We thank Tatyana Kalymbetova for the translation of an article from Russian to English.  ... 
doi:10.1038/srep38870 pmid:27941909 pmcid:PMC5151018 fatcat:lb774dviyjfwhmuyo5zetdakri

Function of alternative splicing

Olga Kelemen, Paolo Convertini, Zhaiyi Zhang, Yuan Wen, Manli Shen, Marina Falaleeva, Stefan Stamm
2013 Gene  
The overall function of alternative splicing is to increase the diversity of mRNAs expressed from the genome.  ...  Alternative splicing regulates the localization of proteins, their enzymatic properties and their interaction with ligands. In most cases, changes caused by individual splicing isoforms are small.  ...  Acknowledgments This work is supported by NIH RO1 GM083187 and an Endowment of the Universty of Kentucky. We thank Eva R. McEnrue for editorial help.  ... 
doi:10.1016/j.gene.2012.07.083 pmid:22909801 pmcid:PMC5632952 fatcat:4t6cozxi2vffnnkhm6difvwhnu

Dynamic landscape of the local translation at activated synapses

T M Khlebodarova, V V Kogai, E A Trifonova, V A Likhoshvai
2017 Molecular Psychiatry  
We developed a mathematical model of FMRP-dependent regulation of postsynaptic density (PSD) protein synthesis in response to mGluR receptor stimulation and conducted in silico experiments to study the  ...  The modeling results revealed the possibility of generating oscillatory (cyclic and quasi-cyclic), chaotic and even hyperchaotic dynamics of postsynaptic protein synthesis as well as the presence of multiple  ...  We thank Tatyana Kalymbetova for the translation of an article from Russian to English, and Alena Moiseenko for the information support for this study.  ... 
doi:10.1038/mp.2017.245 pmid:29203851 pmcid:PMC5754473 fatcat:slchtuncfrhtrjumzqqgnqnezm

The Resolution of Sexual Antagonism by Gene Duplication

T. Connallon, A. G. Clark
2011 Genetics  
The timescale for these evolutionary transitions is sensitive to a suite of genetic and demographic variables, including allelic dominance, recombination, sex linkage, and population size.  ...  The interaction of these processes-within the explicit context of duplication and sexual antagonism-has yet to be formally described by population genetics theory.  ...  Implications for alternative splicing and speciation: Although we present results within the context of whole gene duplications, they may also apply to the evolution of alternatively spliced exons.  ... 
doi:10.1534/genetics.110.123729 pmid:21220356 pmcid:PMC3063682 fatcat:ory6tl62c5fcxcl4jw745qh5hi

Complex networks in genomics and proteomics [chapter]

Ricard V. Solé, Romualdo Pastor-Satorras
2004 Handbook of Graphs and Networks  
Acknowledgements We thank the members of the Complex Systems Lab for useful discussions. This work has been partially supported by the European Network Contract No.  ...  ERBFMRXCT980183, the European Commission -Fet Open project COSIN IST-2001-33555, a grant PB97-0693 and by the Santa Fe Institute (R. V. S.). R.P.  ...  Alternative splicing expands genome complexity in an extraordinary fashion.  ... 
doi:10.1002/3527602755.ch7 fatcat:4tilcf3gqzddblfzjmpcizzade

SnapShot-Seq: A Method for Extracting Genome-Wide, In Vivo mRNA Dynamics from a Single Total RNA Sample

Jesse M. Gray, David A. Harmin, Sarah A. Boswell, Nicole Cloonan, Thomas E. Mullen, Joseph J. Ling, Nimrod Miller, Scott Kuersten, Yong-Chao Ma, Steven A. McCarroll, Sean M. Grimmond, Michael Springer (+1 others)
2014 PLoS ONE  
SnapShot-Seq can detect in vivo changes in the rates of specific steps of splicing, and it provides genome-wide estimates of pre-mRNA synthesis rates comparable to those obtained via labeling of newly  ...  Here we report the development of SnapShot-Seq, a set of computational methods that allow the determination of in vivo rates of pre-mRNA synthesis, splicing, intron degradation, and mRNA decay from a single  ...  There are two scenarios: one where the alternative splice-site shortens the intron, and one where it lengths in the intron.  ... 
doi:10.1371/journal.pone.0089673 pmid:24586954 pmcid:PMC3935918 fatcat:57rrar4hbbbpzkg3xwaju3wgcq

Gene regulation by sense-antisense overlap of polyadenylation signals

R. Gu, Z. Zhang, J. N. DeCerbo, G. G. Carmichael
2009 RNA: A publication of the RNA Society  
Embedded in these late pre-mRNAs are sequences complementary to the early RNAs that act to down-regulate early gene expression via A-to-I editing of dsRNAs.  ...  The model system employed is the mouse polyomavirus. The early and late genes of polyomavirus are transcribed from opposite strands of the circular viral genome.  ...  The early genes encoding large, middle, and small T antigens are expressed by alternative splicing of early-strand transcripts.  ... 
doi:10.1261/rna.1608909 pmid:19390116 pmcid:PMC2685520 fatcat:rux5ydcaafaaxjq2g6xfe5rcxm

Evidence of abundant stop codon readthrough in Drosophila and other metazoa

I. Jungreis, M. F. Lin, R. Spokony, C. S. Chan, N. Negre, A. Victorsen, K. P. White, M. Kellis
2011 Genome Research  
We report an expanded set of 283 readthrough candidates, including 16 double-readthrough candidates; these were manually curated to rule out alternatives such as A-to-I editing, alternative splicing, dicistronic  ...  We previously used comparative genomics evidence to recognize protein-coding regions in 12 species of Drosophila and showed that for 149 genes, the open reading frame following the stop codon has a protein-coding  ...  Gelbart for suggesting this line of investigation during the 12 flies project; the members of the modENCODE project for early release of data; members of and Ensembl for access to SNP data from  ... 
doi:10.1101/gr.119974.110 pmid:21994247 pmcid:PMC3227100 fatcat:42rzpknhajdhjk2bxffom724b4

A decade and a half of protein intrinsic disorder: Biology still waits for physics

Vladimir N. Uversky
2013 Protein Science  
They are very flexible, but some may undergo disorder to order transitions in the presence of natural ligands. The degree of these structural rearrangements varies over a very wide range.  ...  When lacking proper control, they have multiple roles in pathogenesis of various human diseases.  ...  Over the years I collaborated with more than 550 colleagues around the globe, and I am grateful to all former and current colleagues for their priceless contributions, assistance and support.  ... 
doi:10.1002/pro.2261 pmid:23553817 pmcid:PMC3690711 fatcat:ekmtqtyfvbgp3hbbwwqyuddu5m

Intrinsically Disordered Proteins and Their "Mysterious" (Meta)Physics

Vladimir N. Uversky
2019 Frontiers in Physics  
However, by virtue of their existence, IDPs/IDPRs, which are characterized by remarkable conformational flexibility and structural plasticity, break multiple rules established over the years to explain  ...  In this article, some of the wonders of intrinsic disorder are discussed as illustrations of their "mysterious" (meta)physics.  ...  ACKNOWLEDGMENTS I am thankful to Alexey Uversky for careful reading and editing of this manuscript.  ... 
doi:10.3389/fphy.2019.00010 fatcat:c5lhutfmgnc6vcdpw6ybif4eqi

Benchmarking tools for the alignment of functional noncoding DNA

Daniel A Pollard, Casey M Bergman, Jens Stoye, Susan E Celniker, Michael B Eisen
2004 BMC Bioinformatics  
BlastZ, Chaos, ClustalW, DiAlign, Lagan, Needle, and WABA) to determine the off-the-shelf performance of each tool.  ...  As expected, the ability to align noncoding sequences accurately decreases with increasing divergence for all tools, and declines faster in the presence of insertion/deletion evolution.  ...  MBE is a Pew Scholar in the Biomedical Sciences. Research was conducted at the Lawrence Berkeley National Laboratory under Department of Energy contract DE-AC0376SF00098.  ... 
doi:10.1186/1471-2105-5-6 pmid:14736341 pmcid:PMC344529 fatcat:gcdsraimxnd7rcvieaci3teqiq
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