February 2009 Volume 11 Number 2, pp 111 - 226
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Nature Insight RNA silencing
This Nature Insight is a collection of topical reviews on several rapidly moving
areas of RNA silencing. The processing events that give rise to the small RNAs
and the structures of the protein complexes that give them regulatory function
are discussed. Other reviews explore biological aspects of how small viral RNAs
affect virus viability and host cell response, and how small RNAs regulate the
formation and maintenance of silenced chromatin.
Finally, the progress of oligonucleotide therapies that exploit RNA silencing
pathways is summarized.
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----------------------
EDITORIAL
----------------------
Darwin's legacy p111
The double anniversary of Darwin's bicentenary and 150 years since
publication of On the Origin of Species by Means of Natural Selection
provides the perfect pretext to enhance the public understanding of evolution.
doi:10.1038/ncb0209-111
http://www.nature.com/ncb/journal/v11/n2/full/ncb0209-111.html
----------------------
NEWS AND VIEWS
----------------------
Cytokinesis: mind the GAP pp112 - 114
Cytokinesis ensures proper partitioning of genomic and cytoplasmic
material between dividing cells. A key regulator of this process is the
centralspindlin complex. Two recent papers report that GAP activity of
one of the members of this complex regulates the function of Rho
family GTPases during cytokinesis.
Pier Paolo D'Avino and David M. Glover
doi:10.1038/ncb0209-112
http://www.nature.com/ncb/journal/v11/n2/full/ncb0209-112.html
Alzheimer's dementia by circulation disorders: when trees hide the forest
pp114 - 116
Deposition of amyloid beta-peptide in cerebral vessel walls, termed
cerebral amyloid angiopathy (CAA), enhances the cognitive deficits
associated with Alzheimer's disease. The molecular details by which
circulatory defects with hypoxia alter peptide clearance, contributing to
brain deposition and AD, are beginning to be elucidated.
Carlos G. Dotti and Bart De Strooper
doi:10.1038/ncb0209-114
http://www.nature.com/ncb/journal/v11/n2/full/ncb0209-114.html
Linear polyubiquitylation: the missing link in NF-kappaB signalling
pp116 - 118
Metazoan cells respond to external stress or infection through
multiple signalling pathways that converge on NF-kappaB activation,
initiating a program designed to promote survival or trigger cell death.
Recent evidence reveals a mechanism for NF-kappaB activation that
requires assembly of linear polyubiquitin chains as scaffolds to recruit
the activation complex.
Arthur L. Haas
doi:10.1038/ncb0209-116
http://www.nature.com/ncb/journal/v11/n2/full/ncb0209-116.html
Casting back to stem cells pp118 - 120
In the classical view, adult stem cells and their differentiating progeny
are considered to be distinct entities in an irreversible sequence of
development. However, emerging evidence suggests that this distinction
may not be so definitive. Recent work in the mouse shows that a population
of differentiating spermatogonia, when transplanted, can 'de-differentiate'
into functional self-renewing stem cells.
Shosei Yoshida
doi:10.1038/ncb0209-118
http://www.nature.com/ncb/journal/v11/n2/full/ncb0209-118.html
----------------------
RESEARCH HIGHLIGHTS
----------------------
Research highlights p121
Silvia Grisendi, Nathalie Le Bot, Christina Karlsson Rosenthal and
Sowmya Swaminathan
doi:10.1038/ncb0209-121
http://www.nature.com/ncb/journal/v11/n2/full/ncb0209-121.html
----------------------
ARTICLES
----------------------
Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation
pp123 - 132
NF-kappaB signalling protein NEMO is the first physiological substrate
for linear head-to-tail polyubiquitin chains. The heterodimeric ubiquitin
ligase LUBAC catalyses the reaction and mice lacking a LUBAC subunit
show defects in NF-kappaB signalling.
Fuminori Tokunaga et al.
doi:10.1038/ncb1821
Abstract: http://links.ealert.nature.com/ctt?kn=112&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1821.html
The prolyl-isomerase Pin1 is a Notch1 target that enhances Notch1
activation in cancer pp133 - 142
Pin1 interacts with Notch1 to increases its cleavage by gamma-secretase
and thus its transcriptional activity. In a feedback loop, Notch1 controls
Pin1 expression, which results in enhanced Notch1 tumorigenic activity.
Alessandra Rustighi et al.
doi:10.1038/ncb1822
Abstract: http://links.ealert.nature.com/ctt?kn=50&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1822.html
SRF and myocardin regulate LRP-mediated amyloid-[beta] clearance in
brain vascular cells pp143 - 153
Accumulation of amyloid beta peptide in cerebral blood vessels has been
linked to brain dysfunction. SRF and myocardin transcription factors are
induced by cerebral hypoxia and reduce amyloid clearance by regulating
SREBP2, a transcriptional repressor that acts on the amyloid aggregate
clearance factor LRP1.
Robert D. Bell et al.
doi:10.1038/ncb1819
Abstract: http://links.ealert.nature.com/ctt?kn=101&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1819.html
Interaction between TAK1-TAB1-TAB2 and RCAN1-calcineurin defines a
signalling nodal control point pp154 - 161
RCAN1, the regulator of calcineurin phosphatase, interacts with TAK1
kinase binding protein 2 (TAB2). This leads to formation of the signalling
complex TAK1-TAB1-TAB2, which phosphorylates RCAN1 and converts
it to an activator of the calcineurin-NFAT pathway. Activated calcineurin
then switches the signal off by dephopshorylating TAK1 and TAB1.
Qinghang Liu, Jennifer Caldwell Busby and Jeffery D. Molkentin
doi:10.1038/ncb1823
Abstract: http://links.ealert.nature.com/ctt?kn=55&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1823.html
Nuclear signalling by tumour-associated antigen EpCAM pp162 - 171
The intracellular fragment of the adhesion molecule EpCAM, which is
generated by the proteases TACE and presenilin-2, increases cell proliferation
and acts in a complex with beta-catenin and Lef-1 to regulate gene expression.
Dorothea Maetzel et al.
doi:10.1038/ncb1824
Abstract: http://links.ealert.nature.com/ctt?kn=1&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1824.html
CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment
during early embryogenesis pp172 - 182
The DNA-binding chromodomain helicase CHD8 regulates gene expression
but how it acts on specific genes has been unclear. During early embryogenesis
in mice, CHD8 recruits histone H1 to the p53-dependent promotors of apoptotic
genes and thereby prevents massive cell death at this stage of development.
Masaaki Nishiyama et al.
doi:10.1038/ncb1831
Abstract: http://links.ealert.nature.com/ctt?kn=98&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1831.html
----------------------
LETTERS
----------------------
UNC-6 (netrin) orients the invasive membrane of the anchor cell in C. elegans
pp183 - 189
The C.elegans anchor cell is a model for cellular invasion through the basement
membrane. Now netrin (UNC-6) is found to polarize the actin regulators
Ena/VASP and PtdIns (4,5)P2 towards the basement membrane to promote
anchor cell invasion.
Joshua W. Ziel, Elliott J. Hagedorn, Anjon Audhya and David R. Sherwood
doi:10.1038/ncb1825
Abstract: http://links.ealert.nature.com/ctt?kn=8&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1825.html
Mouse differentiating spermatogonia can generate germinal stem cells in vivo
pp190 - 196
When transplanted into adult mice, purified mouse spermatogonial progenitors
that are committed to differentiation can revert to functional germinal stem cells,
with the ability to repopulate germ-cell-depleted testes.
Vilma Barroca et al.
doi:10.1038/ncb1826
Abstract: http://links.ealert.nature.com/ctt?kn=59&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1826.html
Reprogramming of fibroblasts into induced pluripotent stem cells with
orphan nuclear receptor Esrrb pp197 - 203
The orphan nuclear receptor Esrrb induces reprogramming of mouse
embryonic fibroblasts to pluripotent stem cells in cooperation with Oct4
and Sox2.
Bo Feng et al.
doi:10.1038/ncb1827
Abstract: http://links.ealert.nature.com/ctt?kn=74&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1827.html
Topoisomerase II[alpha] controls the decatenation checkpoint
pp204 - 210
Separation of intertwined sister chromatids, mediated by topoisomerase II,
is essential for mitosis. In a separate mechanism, phosphorylation of
topoisomerase II at Ser 1524 during the G2/M phase of the cell cycle
recruits MDC1 to activate the decatenation checkpoint required for
genomic stability.
Kuntian Luo, Jian Yuan, Junjie Chen and Zhenkun Lou
doi:10.1038/ncb1828
Abstract: http://links.ealert.nature.com/ctt?kn=100&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1828.html
Phosphorylation of ATM by Cdk5 mediates DNA damage signalling and
regulates neuronal death pp211 - 218
CDK5 kinase regulates the neuronal stress response, whereas the DNA
damage response kinase ATM induces apoptosis in postmitotic neurons.
Now, CDK5 activated by DNA damage is shown to directly activate ATM to
induce neuronal cell death.
Bo Tian, Qian Yang and Zixu Mao
doi:10.1038/ncb1829
Abstract: http://links.ealert.nature.com/ctt?kn=22&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1829.html
Cytoplasmic penetration and persistent infection of mammalian cells by
polyglutamine aggregates pp219 - 225
Fibrillar polyglutamine aggregates are taken up by mammalian cells in
culture and associate with aggresomes that contain both proteasome
subunits and chaperones. Aggresomes also recruit soluble proteins that
share the same amyloidogenic sequences as the internalised polyglutamine
aggregates.
Pei-Hsien Ren et al.
doi:10.1038/ncb1830
Abstract: http://links.ealert.nature.com/ctt?kn=3&m=31243278&r=MTc2NDEyMTk0MQS2&b=2&j=NDU1Mjk4MjAS1&mt=1&rt=0
Article: http://www.nature.com/ncb/journal/v11/n2/full/ncb1830.html
----------------------
ERRATUM
----------------------
Apoptotic histone modification inhibits nuclear transport by regulating RCC1
p226
Chi-Hang Wong et al.
doi:10.1038/ncb0209-226
http://www.nature.com/ncb/journal/v11/n2/full/ncb0209-226.html
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Poster on Production and Actions of Small RNAs
Recent progress in cloning, deep sequencing and bioinformatics have revealed an
astounding landscape of small RNAs in eukaryotic cells. This Poster by V. Narry Kim
and Mikiko C. Siomi depicts our current understanding of the processing pathways of
eukaryotic small RNAs and their possible mechanisms of action.
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