Mystery at the heart of life

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December 21, 2014

Cell biology, Intelligent Design, News

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Cell biology
Intelligent Design
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By Biologic Institute’s Ann Gauger, at Christianity Today’s Behemoth, the secret life of cells:

Our bodies are made up of some 100 trillion cells. We tend to think of cells as static, because that’s how they were presented to us in textbooks. In fact, the cell is like the most antic, madcap, crowded (yet fantastically efficient) city you can picture. And at its heart lies a mystery—or I should say, several mysteries—involving three special kinds of molecules: DNA, RNA, and proteins.

These molecules are assembled into long chains called polymers, and are uniquely suited for the roles they play. More importantly, life absolutely depends upon them. We have to have DNA, RNA, and protein all present and active at the same time for a living organism to live.

How they work together so optimally and efficiently is not merely amazing, but also a great enigma, a mystery that lies at the heart of life itself. More. Paywall soon after. May be worth it.

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Whether the physicochemical and nutritional properties can explain the distinctive nutritional, sensory and metabolic characteristics among the different milks requires further studies.
Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota Giovanna Trinchese, Gina Cavaliere, Roberto Berni Canani, Sebastien Matamoros, Paolo Bergamo, Chiara De Filippo, Serena Aceto, Marcello Gaita, Pellegrino Cerino, Rossella Negri, Luigi Greco, Patrice D. Cani, Maria Pina Mollica doi:10.1016/j.jnutbio.2015.05.003 The Journal of Nutritional Biochemistry Volume 26, Issue 11, Pages 1136–1146 http://www.sciencedirect.com/science/article/pii/S0955286315001369

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[...] the Skeletor/Megator/Chromator proteins complex together and subsequently support a spindle envelope independent of microtubules. The spindle envelope excludes large membrane-bound organelles, leading to increased concentration of mitotic reaction constituents and thus ultimately catalyzing cell division. It will be exciting in the future to determine if the spindle area is indeed subject to molecular crowding in the purest of forms (solvent exclusion) and how this effect drives cell division.
Concentrating on the mitotic spindle Paul S. Maddox and Anne-Marie Ladouceur JCB vol. 210 no. 5 691-693 The Rockefeller University Press, doi: 10.1083/jcb.201508007 http://jcb.rupress.org/content/210/5/691.full?trendmd-shared=0

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The mitotic spindle is a microtubular assembly required for chromosome segregation during mitosis. Additionally, a spindle matrix has long been proposed to assist this process, but its nature has remained elusive. [...] we uncovered a microtubule-independent mechanism that underlies the accumulation of molecules in the spindle region. This mechanism relies on a membranous system surrounding the mitotic spindle that defines an organelle-exclusion zone that is conserved in human cells. [...] organelle exclusion by a membrane system causes spatio-temporal differences in molecular crowding states that are sufficient to drive accumulation of mitotic regulators, such as Mad2 and Megator/Tpr, as well as soluble tubulin, in the spindle region. This membranous “spindle envelope” confined spindle assembly, and its mechanical disruption compromised faithful chromosome segregation. Thus, cytoplasmic compartmentalization persists during early mitosis to promote spindle assembly and function.
An organelle-exclusion envelope assists mitosis and underlies distinct molecular crowding in the spindle region Nina Schweizer, Nisha Pawar, Matthias Weiss and Helder Maiato JCB vol. 210 no. 5 695-704 The Rockefeller University Press, doi: 10.1083/jcb.201506107 http://jcb.rupress.org/content/210/5/695.abstract

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Cell biology is a rapidly advancing field, and new observations frequently disprove mechanistic hypotheses after just a few short years. Yet, nothing that we have learned about mitosis in the last 30 years, which includes the discovery of scores of factors involved in spindle assembly, has been inconsistent with the basic principles of S&C. Instead, the many facilitating mechanisms elucidated over the years have been organically incorporated into the model. It is important to emphasize that these mechanisms are often not essential: spindles form in the absence of mitotic gradients (Maresca et al., 2009), or when the function of key motors is blocked (Ganem et al., 2005; Gayek and Ohi, 2014) or spindle geometry is perturbed (Ganem et al., 2009; Silkworth et al., 2009; Lancaster et al., 2013). As long as the minimal requirements for S&C (i.e., dynamic microtubules and capture by kinetochores) are in place, a functional spindle can assemble. However, the duration of spindle assembly and the number of erroneous chromosome attachments increase dramatically in the absence of facilitating S&C mechanisms. Importantly, both of these side effects compromise the fate of daughter cells: the prolongation of mitosis has been shown to halt progression through the ensuing cell cycle (Uetake and Sluder, 2010), and erroneous segregation of a chromosome can trigger perpetuating chromosomal instability (Thompson and Compton, 2008). Thus, the complexity of numerous nonessential mechanisms sustains the wonderfully simple principle of S&C.
Thirty years of search and capture: The complex simplicity of mitotic spindle assembly Rebecca Heald and Alexey Khodjakov JCB vol. 211 no. 6 1103-1111 The Rockefeller University Press, doi: 10.1083/jcb.201510015 http://jcb.rupress.org/content/211/6/1103.full?sid=ab94d7c5-1818-4a2a-a121-cc8d45e095d1

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During mammalian T cell development, the requirement for expansion of many individual T cell clones, rather than merely expansion of the entire T cell population, suggests a possible role for asymmetric cell division (ACD). We show that ACD of developing T cells controls cell fate through differential inheritance of cell fate determinants Numb and ?-Adaptin. ACD occurs specifically during the ?-selection stage of T cell development, and subsequent divisions are predominantly symmetric. ACD is controlled by interaction with stromal cells and chemokine receptor signaling and uses a conserved network of polarity regulators. The disruption of polarity by deletion of the polarity regulator, Scribble, or the altered inheritance of fate determinants impacts subsequent fate decisions to influence the numbers of DN4 cells arising after the ?-selection checkpoint. These findings indicate that ACD enables the thymic microenvironment to orchestrate fate decisions related to differentiation and self-renewal.
Asymmetric cell division during T cell development controls downstream fate Kim Pham, Raz Shimoni, Mirren Charnley, Mandy J. Ludford-Menting, Edwin D. Hawkins, Kelly Ramsbottom, Jane Oliaro, David Izon, Stephen B. Ting, Joseph Reynolds, Grant Lythe, Carmen Molina-Paris, Heather Melichar, Ellen Robey, Patrick O. Humbert, Min Gu and Sarah M. Russell JCB vol. 210 no. 6 933-950 The Rockefeller University Press, doi: 10.1083/jcb.201502053 http://jcb.rupress.org/content/210/6/933?cited-by=yes&legid=jcb;210/6/933

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MG act like taut springs that protect the neural tissue from ripping apart by holding the neural layers together. How MG provide tensile strength is yet unclear. It would therefore be interesting to examine whether glial cells elsewhere in the brain also provide mechanical resilience to neural structures. Our study demonstrates that at least one type of glial cell, the MG in the retina, do indeed act like “nerve putty” and physically support neurons in vivo.
Müller glia provide essential tensile strength to the developing retina Ryan B. MacDonald, Owen Randlett, Julia Oswald, Takeshi Yoshimatsu, Kristian Franze and William A. Harris JCB vol. 210 no. 7 1075-1083 The Rockefeller University Press, doi: 10.1083/jcb.201503115 http://jcb.rupress.org/content/210/7/1075.full?trendmd-shared=0

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The nervous system is one of the softest tissues in the body, with a consistency similar to that of cream cheese. Yet it is also the most highly organized tissue in the body, composed of neurons and glial cells arranged into discrete layers. How this incredibly soft and complex tissue maintains its integrity throughout life, despite the many physical stresses imparted on it, remains a mystery.
Müller glia provide essential tensile strength to the developing retina Ryan B. MacDonald, Owen Randlett, Julia Oswald, Takeshi Yoshimatsu, Kristian Franze and William A. Harris JCB vol. 210 no. 7 1075-1083 The Rockefeller University Press, doi: 10.1083/jcb.201503115 http://jcb.rupress.org/content/210/7/1075.full?trendmd-shared=0

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Notch family members are transmembrane receptors that mediate essential developmental programs. Upon ligand binding, a proteolytic event releases the intracellular domain of Notch, which translocates to the nucleus to regulate gene transcription. In addition, Notch trafficking across the endolysosomal system is critical in its regulation. In this study we report that Notch recycling to the cell surface is dependent on the COMMD–CCDC22–CCDC93 (CCC) complex, a recently identified regulator of endosomal trafficking. Disruption in this system leads to intracellular accumulation of Notch2 and concomitant reduction in Notch signaling. Interestingly, among the 10 copper metabolism MURR1 domain containing (COMMD) family members that can associate with the CCC complex, only COMMD9 and its binding partner, COMMD5, have substantial effects on Notch. Furthermore, Commd9 deletion in mice leads to embryonic lethality and complex cardiovascular alterations that bear hallmarks of Notch deficiency. Altogether, these studies highlight that the CCC complex controls Notch activation by modulating its intracellular trafficking and demonstrate cargo-specific effects for members of the COMMD protein family.
Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling Haiying Li, Yeon Koo, Xicheng Mao, Luis Sifuentes-Dominguez, Lindsey L. Morris, Da Jia, Naoteru Miyata, Rebecca A. Faulkner, Jan M. van Deursen Marc Vooijs, Daniel D. Billadeau, Bart van de Sluis, Ondine Cleaver and Ezra Burstein JCB Home > 2015 Archive > Li et al. 211 (3): 605 JCB vol. 211 no. 3 605-617 The Rockefeller University Press, doi: 10.1083/jcb.201505108 http://jcb.rupress.org/content/211/3/605.abstract

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[...] the mechanism of asymmetric endosome segregation is not understood. Our data uncover the molecular and physical mechanism by which organelles localized away from the cellular cortex can be dispatched asymmetrically during asymmetric division.
Polarized endosome dynamics by spindle asymmetry during asymmetric cell division Emmanuel Derivery, Carole Seum, Alicia Daeden, Sylvain Loubéry, Laurent Holtzer, Frank Jülicher & Marcos Gonzalez-Gaitan Nature 528, 280–285 doi:10.1038/nature16443 http://www.nature.com/nature/journal/v528/n7581/full/nature16443.html

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The underlying molecular basis of this effect is poorly understood. [...] our discovery [...] provides new insights into how the environment affects animal physiology. The significance to the animal of cold-induced stimulation of IPCs and expression of dilps is an intriguing question. [...] we are unable to tell which subgroup of neurons is involved in cold regulation of growth and which is not [...] [...] other, as yet unidentified, cold-sensing neurons must also play a significant role in transmitting cold signals to IPCs and, thereby, modulating growth. [...] distinct mechanisms regulate the delay in pupariation and the enhancement in pupal size induced by cold temperature. [...] dilp8 [...] might serve as the molecular mediator of cold-induced developmental delay. However, more work will be needed to clarify this issue.
Cold-sensing regulates Drosophila growth through insulin-producing cells Qiaoran Li & Zhefeng Gong Nature Communications 6, Article number: 10083 doi:10.1038/ncomms10083

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One of the principal findings of this study is the discovery of 77 enhancers that exhibit a remarkably diverse range of cis-regulatory activities during embryonic and postembryonic development. The biological significance of this enhancer diversity most likely reflects the diversity of the developmental programs in which these transcription factors participate. We also identified functionally related enhancers that share multiple conserved DNA sequences and determined that these enhancers could be classified using hierarchical clustering techniques. In addition, our analysis has revealed that the collinearity between the pdm genes is predominantly confined to their POU domain and homeodomain exons, suggesting that their noncoding sequences are diverging at a faster rate than their coding sequences. These results should provide further insight into the regulatory logic that controls cis-regulatory function and thus gene regulation.
cis-regulatory analysis of the Drosophila pdm locus reveals a diversity of neural enhancers Jermaine Ross, Alexander Kuzin, Thomas Brody and Ward F. Odenwald BMC Genomics201516:700 DOI: 10.1186/s12864-015-1897-2 © Ross et al. 2015 http://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-015-1897-2

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While further work is required to determine whether these shared elements are important for enhancer activity, these findings suggest a level of structural complexity in the presence and clustering of enhancers that requires further analysis. To construct a better representation of enhancer structure and thus cis-regulatory prediction, one would ideally prefer to use a larger training set of enhancers to improve the accuracy of prediction. These approaches will be addressed in future studies.
cis-regulatory analysis of the Drosophila pdm locus reveals a diversity of neural enhancers Jermaine Ross, Alexander Kuzin, Thomas Brody and Ward F. Odenwald BMC Genomics201516:700 DOI: 10.1186/s12864-015-1897-2 © Ross et al. 2015 http://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-015-1897-2

[emphasis mine] Complex complexity Work in progress... stay tunedDionisio_{January 1, 2016
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It remains to be understood how decisions are made and behavioural responses coordinated at far and near distances, as a pollinator moves between flowers, approaches and visits them.
More than colour attraction: behavioural functions of flower patterns Natalie Hempel de Ibarra, Keri V Langridge, Misha Vorobyev doi:10.1016/j.cois.2015.09.005 Current Opinion in Insect Science Volume 12, Pages 64–70 Neuroscience * Special Section: Insect conservation http://www.sciencedirect.com/science/article/pii/S2214574515001364

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Polyphenism is a form of developmental plasticity in which organisms respond to environmental cues by producing adaptive, discrete, alternative phenotypes known as morphs. [...] integration of multilayered approaches will be necessary to understand the complex mechanisms involved in regulating alternative morphologies
The right tools for the job: regulating polyphenic morph development in insects Jennifer A Brisson, Gregory K Davis doi:10.1016/j.cois.2015.09.011 Current Opinion in Insect Science Volume 13, Pages 1–6 http://www.sciencedirect.com/science/article/pii/S221457451500142X

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Adult stem cells continuously undergo self-renewal and generate differentiated cells. Compared to the self-renewing niche, relatively little is known about the maintenance and function of the differentiation niche. [...] this study has revealed a novel strategy for Wnt signaling in regulating the cellular redox state and maintaining the differentiation niche. Although the differentiation niche is critical for promoting GSC progeny differentiation, little is known about its regulation. future research will be needed to investigate the molecular mechanisms for Wnt signaling in the differentiation niche to prevent BMP signaling and maintain long ISC cellular processes.
Wnt signaling-mediated redox regulation maintains the germ line stem cell differentiation niche Su Wang, Yuan Gao, Xiaoqing Song, Xing Ma, Xiujuan Zhu, Ying Mao, Zhihao Yang, Jianquan Ni, Hua Li, Kathryn E Malanowski, Perera Anoja, Jungeun Park, Jeff Haug, Ting Xie DOI: http://dx.doi.org/10.7554/eLife.08174 eLife 2015;4:e08174 http://elifesciences.org/content/4/e08174

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Identifying RNA targets for RBPs is critical to gain a mechanistic understanding of how these RBPs help shape the developing brain. Future studies which couple optimized RNA immunoprecipitation approaches with single cell resolution will be ideal. The future is exciting for RNA regulation in corticogenesis as the advent of new technologies will lead to great advances in this field of research.
Post-transcriptional regulation in corticogenesis: how RNA-binding proteins help build the brain Louis-Jan Pilaz and Debra L. Silver DOI: 10.1002/wrna.1289 Wiley Interdisciplinary Reviews: RNA Volume 6, Issue 5, pages 501–515 http://onlinelibrary.wiley.com/doi/10.1002/wrna.1289/abstract

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[...] we have just scratched the surface in terms of a comprehensive understanding of how RBPs influence cortical development and which RBPs are important. [...] virtually all aspects of posttranscriptional regulation are implicated in corticogenesis. Many fundamental questions now remain to be answered. Answering these questions in a complex tissue such as the embryonic mammalian cortex is challenging and will require multidisciplinary approaches encompassing bioinformatics, biochemistry, and genetics.
Post-transcriptional regulation in corticogenesis: how RNA-binding proteins help build the brain Louis-Jan Pilaz and Debra L. Silver DOI: 10.1002/wrna.1289 Wiley Interdisciplinary Reviews: RNA Volume 6, Issue 5, pages 501–515 http://onlinelibrary.wiley.com/doi/10.1002/wrna.1289/abstract

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[...] RNA localization may serve as a cell fate determinant to help two daughter cells adopt different fates. This mechanism involves a multistep process [...] Future studies and identification of asymmetrically localized mRNAs and RBPs in mitotic neural progenitors will help define whether this mechanism is broadly used for cell fate determination in the mammalian cortex.
Post-transcriptional regulation in corticogenesis: how RNA-binding proteins help build the brain Louis-Jan Pilaz and Debra L. Silver DOI: 10.1002/wrna.1289 Wiley Interdisciplinary Reviews: RNA Volume 6, Issue 5, pages 501–515 http://onlinelibrary.wiley.com/doi/10.1002/wrna.1289/abstract

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Given the complexity of the developing mammalian cortex, a major challenge for the future will be to understand how dynamic RNA regulation occurs within heterogeneous cell populations, across space and time. In sum, post-transcriptional regulation has emerged as a critical mechanism for driving corticogenesis and exciting direction of future research.
Post-transcriptional regulation in corticogenesis: how RNA-binding proteins help build the brain Louis-Jan Pilaz and Debra L. Silver DOI: 10.1002/wrna.1289 Wiley Interdisciplinary Reviews: RNA Volume 6, Issue 5, pages 501–515 http://onlinelibrary.wiley.com/doi/10.1002/wrna.1289/abstract

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Note that posts @1464-1470 point to a very juicy paper that raises several interesting questions. Definitely complex complexity. Work in progress... stay tuned.Dionisio_{December 29, 2015
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[...] the high number of translated uORFs within the core clock transcripts is particularly striking. uORF translation [...] represents an attractive mechanism for how clock protein levels (and consequently clock parameters) could be adjusted post-transcriptionally. It is tempting to speculate that one or several of the identified core clock uORFs are implicated in the short period phenotype observed in Denr-depleted cells. [...] there is growing evidence for cell-type–specific uORF usage [...] and it is also largely unexplained how certain core clock parameters can be strikingly tissue specific [...] It is conceivable that cell-type–specific differences in clock protein concentration and/or stoichiometry are involved [...] that tissue-specific uORF usage and translation rates contribute. [...] the circadian system represents a particularly suitable paradigm for future studies of uORF biology.
Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames Peggy Janich, Alaaddin Bulak Arpat, Violeta Castelo-Szekely, Maykel Lopes1 and David Garfield doi: 10.1101/gr.195404.115 Genome Res. 2015. 25: 1848-1859 http://genome.cshlp.org/content/25/12/1848.full

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[...] our study has unveiled important insights into how translation contributes to core clock regulation. [...] the CDS-mapping RPF-seq reads allow estimating relative biosynthesis rates of core clock proteins, which will likely add to a better quantitative understanding of the clock mechanism. [...] the footprint profiles from several clock mRNAs showed hallmarks of regulation that, however, may be operative not in a temporal fashion but under other (e.g., environmental, metabolic, cell-type–specific) conditions yet to be defined.
Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames Peggy Janich, Alaaddin Bulak Arpat, Violeta Castelo-Szekely, Maykel Lopes1 and David Garfield doi: 10.1101/gr.195404.115 Genome Res. 2015. 25: 1848-1859 http://genome.cshlp.org/content/25/12/1848.full

[emphasis mine] Complex complexity Work in progress... stay tunedDionisio_{December 29, 2015
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It is noteworthy that clock genes showed constant TEs, indicating exclusion from time of day–dependent translational control. The considerable delays between mRNA and protein accumulation that have been reported for several core clock components [...] must therefore have other, post-translational origins.
Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames Peggy Janich, Alaaddin Bulak Arpat, Violeta Castelo-Szekely, Maykel Lopes1 and David Garfield doi: 10.1101/gr.195404.115 Genome Res. 2015. 25: 1848-1859 http://genome.cshlp.org/content/25/12/1848.full

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Many translationally regulated transcripts are hence not covered by the proteome data. Transcripts encoding components of the protein biosynthesis machinery stand out among the rhythmically translated mRNAs. [...] the mechanism entails more than a simple, immediate reaction to nutrients. [...] the relatively variable up-regulation seen across biological replicates [...] is remarkable for genetically identical animals and could point to a behavioral component contributing to the regulatory mechanism. It remains to be explored whether this similarity is indicative of mechanistic parallels. Another exciting open question concerns the possibility that the rhythmic biosynthesis of components of the translational apparatus contributes to daily changes in overall translation rate [...] [...] the rhythmic regulation of IRE-containing transcripts uncovers a previously unappreciated extent of temporal control in this physiologically important pathway.
Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames Peggy Janich, Alaaddin Bulak Arpat, Violeta Castelo-Szekely, Maykel Lopes1 and David Garfield doi: 10.1101/gr.195404.115 Genome Res. 2015. 25: 1848-1859 http://genome.cshlp.org/content/25/12/1848.full

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How translation efficiency contributes to temporal gene expression is a largely unexplored facet of chronobiology. Translation is one step closer than the mRNA to the relevant output of most gene expression, the protein. [...] the true extent of translationally driven rhythmicity may even be higher. How does the translatome data correlate with the rhythmic proteome? The answer to this question is less straightforward than expected.
Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames Peggy Janich, Alaaddin Bulak Arpat, Violeta Castelo-Szekely, Maykel Lopes1 and David Garfield doi: 10.1101/gr.195404.115 Genome Res. 2015. 25: 1848-1859 http://genome.cshlp.org/content/25/12/1848.full

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The mammalian circadian system consists of a master pacemaker in the brain's suprachiasmatic nuclei (SCN) that synchronizes subsidiary oscillators present in most cell types. [...] a comprehensive and quantitative analysis of rhythmic translation from a mammalian organ is still lacking.
Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames Peggy Janich, Alaaddin Bulak Arpat, Violeta Castelo-Szekely, Maykel Lopes1 and David Garfield doi: 10.1101/gr.195404.115 Genome Res. 2015. 25: 1848-1859 http://genome.cshlp.org/content/25/12/1848.full

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Mammalian gene expression displays widespread circadian oscillations. Rhythmic transcription underlies the core clock mechanism, but it cannot explain numerous observations made at the level of protein rhythmicity. In summary, our data offer a framework for understanding the dynamics of translational regulation, circadian gene expression, and metabolic control in a solid mammalian organ.
Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames Peggy Janich, Alaaddin Bulak Arpat, Violeta Castelo-Szekely, Maykel Lopes1 and David Garfield doi: 10.1101/gr.195404.115 Genome Res. 2015. 25: 1848-1859 http://genome.cshlp.org/content/25/12/1848.full

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An important question for future study is to characterize the interactomes and understand regulation by the dozens of other splicing regulators that are not SR proteins or hnRNPs. These factors can often activate or repress splicing with similar frequency, usually in a manner that depends on where they bind in relation to the regulated exons, often described by an ‘RNA map’. For example, several factors might activate exon inclusion when bound downstream of the exon, but might repress splicing when bound upstream. Ultimately, one hopes that our understanding of the splicing interactome will be unified with our understanding of the structures and regulatory functions of individual factors and complexes in order to fully illuminate the underlying mechanisms.
Interactome analysis brings splicing into focus Daniel Dominguez and Christopher B. Burge Genome Biology 2015, 16:135 doi:10.1186/s13059-015-0707-0 http://www.genomebiology.com/2015/16/1/135

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Alternative pre-mRNA splicing is a critical component of the regulation of gene expression pathways in metazoans. Combining alternative exons in different patterns dramatically expands the proteomic of metazoan genomes and contributes significantly to the identity, development, and diversity of cells, tissue, and organs. New breakthroughs in cryo–electron microscopy and image collection will soon lead to improved high-resolution structures of the spliceosome.
Mechanisms and Regulation of Alternative Pre-mRNA Splicing Annual Review of Biochemistry DOI: 10.1146/annurev-biochem-060614-034316 Vol. 84: 291-323 Yeon Lee and Donald C. Rio http://www.annualreviews.org/doi/abs/10.1146/annurev-biochem-060614-034316

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Most RNA-binding proteins bear conserved motifs, known as the RBDs. However, neither the N-terminal region nor the C-terminal region of Gemin5 harbours a canonical RBD. The fifth WD repeat domain has been demonstrated to be involved in the recognition of the snRNP code, as well as in the recognition of the cap. In contrast, a bipartite non-canonical RNA binding domain within the C-terminal region is responsible for the interaction with the IRES element and, moreover, for the negative effect on internal initiation. This non-canonical motif, however, appears to have an intrinsically disorganised structure, which can confer flexibility to the protein and, thus, the possibility to select different conformations depending on the function exerted by the protein. To date, the network of RNAs and proteins interacting with this region of Gemin5 is unknown. Future studies aimed at disclosing these networks will undoubtedly reveal new unanticipated roles of Gemin5 in other cellular processes.
Gemin5: A Multitasking RNA-Binding Protein Involved in Translation Control David Piñeiro 1,*, Javier Fernandez-Chamorro 2, Rosario Francisco-Velilla 2 and Encarna Martinez-Salas 2 Biomolecules 2015, 5(2), 528-544; doi:10.3390/biom5020528 http://www.mdpi.com/2218-273X/5/2/528/htm

Complex complexity Work in progress... stay tunedDionisio_{December 28, 2015
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