February 2010 Volume 17 Number 2, pp 139 - 257
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EDITORIAL
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Scientific writing 101 p139
doi:10.1038/nsmb0210-139
Less is more when it comes to writing a good scientific paper. Tell
a story in clear, simple language and keep in mind the importance of
the 'big picture'.
http://links.ealert.nature.com/ctt?kn=100&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
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NEWS AND VIEWS
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Substrate check of gamma-secretase pp140 - 141
Yun-wu Zhang and Huaxi Xu
doi:10.1038/nsmb0210-140
gamma-secretase cleaves multiple substrates with essential roles
from development to neurodegeneration, and its aberrant processing
underlies human disorders including Alzheimer's disease (AD). Tian
et al. now identify a domain in the beta-amyloid precursor protein
(APP) that inhibits gamma-secretase activity and show that certain
familial AD-linked APP mutations within this domain impair this
inhibition, resulting in increased beta-amyloid generation. The
study thus reveals a novel mechanism whereby gamma-secretase's
activity is influenced by its own substrate.
http://links.ealert.nature.com/ctt?kn=10&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Two ways to misregulate mRNAs in myotonic dystrophy pp141 - 142
Rodger B Voelker and J Andrew Berglund
doi:10.1038/nsmb0210-141
Myotonic dystrophy is caused by expanded CTG repeats, and the
expression of these repeats as RNA leads to the sequestration
of the splicing factor muscleblind-like (MBNL1) to the CUG RNA.
Two mouse models for myotonic dystrophy-mice expressing
expanded CUG repeats and mice lacking functional MBNL1-now reveal
~100 new mis-splicing events and a new class of aberrantly regulated
mRNAs.
http://links.ealert.nature.com/ctt?kn=13&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
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RESEARCH HIGHLIGHTS
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Research highlights p143
doi:10.1038/nsmb0210-143
http://links.ealert.nature.com/ctt?kn=16&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
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ARTICLES
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Allosteric regulation of Argonaute proteins by miRNAs pp144 - 150
Sergej Djuranovic et al.
doi:10.1038/nsmb.1736
Argonaute family members are key effectors of small RNA function.
Predicted structural analogies to allosterically-regulated bacterial
ligand-binding proteins, followed by biochemical analysis of the
binding properties of Argonautes, now indicate functional allostery
between two distinct binding sites that would promote a functional
outcome when both a miRNA and capped mRNA are present.
Abstract: http://links.ealert.nature.com/ctt?kn=34&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=119&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
An APP inhibitory domain containing the Flemish mutation residue
modulates gamma-secretase activity for Abeta production pp151 - 158
Yuan Tian, Bhramdeo Bassit, Deming Chau and Yue-Ming Li
doi:10.1038/nsmb.1743
Among the mutations in the amyloid precursor protein (APP) involved
in familial Alzheimer's disease is the so-called Flemish mutation
(A21G). Now a biochemical study of this mutation reveals the
existence of a domain in APP that binds to an allosterica site in
the gamma-secretase complex and inhibits the enzymatic activity
leading to the production of amyloidogenic peptide Abeta.
Abstract: http://links.ealert.nature.com/ctt?kn=36&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=12&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Alda-1 is an agonist and chemical chaperone for the common human
aldehyde dehydrogenase 2 variant pp159 - 164
Samantha Perez-Miller et al.
doi:10.1038/nsmb.1737
Alcohol dehydrogenase (ALDH2) is involved in metabolising ethanol.
A single point mutation leads to Asian alcohol-induced flushing
syndrome and is linked to increased cardiac damage following a
heart attack. The small molecule Alda-1 restores normal activity
to the mutant, and structures of Alda-1 bound to mutant ALDH2 and
the wild type now explain this effect.
Abstract: http://links.ealert.nature.com/ctt?kn=38&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=113&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Structural basis for dsRNA recognition and interferon antagonism by
Ebola VP35 pp165 - 172
Daisy W Leung et al.
doi:10.1038/nsmb.1765
The protein VP35 from Ebola virus contributes to immune evasion by
antagonizing interferon signaling pathways. Now the crystal structure
of the interferon inhibitory domain of VP35 bound to dsRNA indicates
that VP35 sequesters the dsRNA ends, preventing them from being sensed
by RIG-I-like receptors and inhibiting immune responses.
Abstract: http://links.ealert.nature.com/ctt?kn=40&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=99&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Comprehensive discovery of endogenous Argonaute binding sites in
Caenorhabditis elegans pp173 - 179
Dimitrios G Zisoulis et al.
doi:10.1038/nsmb.1745
MicroRNAs are small RNAs involved in regulation of cognate mRNAs, but
predicting their exact targets has been difficult. Using a
cross-linking immunoprecipitation technique, a comprehensive
examination of endogenous mRNA target sites associated with the
C. elegans Argonaute family member ALG-1 is now presented.
Abstract: http://links.ealert.nature.com/ctt?kn=42&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=92&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Structural basis for the Rho- and phosphoinositide-dependent
localization of the exocyst subunit Sec3 pp180 - 186
Masami Yamashita et al.
doi:10.1038/nsmb.1722
The Sec3 subunit of the yeast exocyst complex tethers secretory
vesicles to the plasma membrane for exocytosis through interactions
with a small GTPase and PtdIns(4,5)P2 in the target membrane. A new
study describes the crystal structure of the N-terminal Rho1/Cdc42-
and PtdIns(4,5)P2-binding domain of Sec3 in complex with Rho1.
Abstract: http://links.ealert.nature.com/ctt?kn=44&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=91&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Aberrant alternative splicing and extracellular matrix gene expression
in mouse models of myotonic dystrophy pp187 - 193
Hongqing Du et al.
doi:10.1038/nsmb.1720
Myotonic dystrophy is a CUG repeat expansion disease and mice
deficient in MBNL1, an RNA binding protein, show many characteristics
of the disease. Comparison of gene expression profiles of two mouse
models of the disease reveals that CUG repeat expansions have two
effects - loss of Mbnl1 function that leads to altered splicing and
loss of an as yet unknown function that disrupts extracellular matrix
protein mRNA regulation.
Abstract: http://links.ealert.nature.com/ctt?kn=46&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=15&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
CDK8 is a positive regulator of transcriptional elongation within the
serum response network pp194 - 201
Aaron J Donner, Christopher C Ebmeier, Dylan J Taatjes and Joaquin
M Espinosa
doi:10.1038/nsmb.1752
CDK8 is a kinase found in some Mediator complexes and has been
implicated in oncogenesis. Now it is shown to be a positive
regulator of transcription elongation at immediate early serum
response genes, regulating recruitment of elongation factors
including P-TEFb.
Abstract: http://links.ealert.nature.com/ctt?kn=48&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=64&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Yeast telomerase subunit Est1p has guanine quadruplex-promoting
activity that is required for telomere elongation pp202 - 209
Ming-Liang Zhang et al.
doi:10.1038/nsmb.1760
The yeast telomerase subunit Est1p has been implicated in recruitment
of the telomerase complex to telomeres via its interaction with Cdc13p,
but genetic data have pointed to an additional role for Est1p in
telomere maintenance. Now Est1p is shown to convert G-rich telomeric
DNA into G-quadruplex structures in vitro, and this activity is
essential for telomere length maintenance in vivo.
Abstract: http://links.ealert.nature.com/ctt?kn=108&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=70&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Crystal structure of an intramolecular chaperone mediating
triple-beta-helix folding pp210 - 215
Eike C Schulz et al.
doi:10.1038/nsmb.1746
Some viral proteins involved in interaction with the host cell
surface adopt a very rigid and stable triple-beta-helix fold.
In order to attain this complex fold, these proteins contain an
intramolecular chaperone domain that is auto-cleaved after assembly.
Now structural work on two such chaperone domains indicates how they
can promote correct folding of the beta-helices.
Abstract: http://links.ealert.nature.com/ctt?kn=105&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=77&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Human PRP4 kinase is required for stable tri-snRNP association during
spliceosomal B complex formation pp216 - 221
Marc Schneider et al.
doi:10.1038/nsmb.1718
Reversible phosphorylation plays a key role in splicing.
Phosphorylation of two splicing components, PRP6 and PRP31,
is now shown to be mediated by PRP4. This activity is involved
in promoting the stable association of the triple-snRNP to form
B complexes, indicating how this kinase promotes building of a
stable, functional spliceosome.
Abstract: http://links.ealert.nature.com/ctt?kn=107&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=54&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
APOBEC3 proteins mediate the clearance of foreign DNA from human
cells pp222 - 229
Mark D Stenglein et al.
doi:10.1038/nsmb.1744
APOBEC3 cytidine deaminases have been implicated in restriction of
retroviruses and retrotransposons in mammalian cells. Now human
APOBEC3A is shown to be upregulated by interferon and to catalyze
the deamination of foreign double-stranded DNA transfected into
primary cells or cell lines, with no detectable effect on genomic DNA.
Abstract: http://links.ealert.nature.com/ctt?kn=103&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=43&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Molecular determinants of coupling between the domain III voltage
sensor and pore of a sodium channel pp230 - 237
Yukiko Muroi, Manoel Arcisio-Miranda, Sandipan Chowdhury and
Baron Chanda
doi:10.1038/nsmb.1749
In voltage-gated sodium channels, a voltage-sensor domain communicates
with the pore gate regions, but the details of this process remain
unclear. Now the electromechanical coupling in a Na+ channel is probed
by tryptophane scanning mutagenesis, together with structural modeling,
with the results indicating a crucial role for the hinge regions.
Abstract: http://links.ealert.nature.com/ctt?kn=104&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=41&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
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BRIEF COMMUNICATIONS
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Structural insights into the human GW182-PABC interaction in
microRNA-mediated deadenylation pp238 - 240
Martin Jinek et al.
doi:10.1038/nsmb.1768
GW182 has been implicated in the effector steps of microRNA-mediated
repression and recently shown to interact with the Poly(A) binding
protein C-terminal domain (PABPC1). The structure of PABPC1 in complex
with a human GW182 paralog peptide, now gives insight into the
interactions needed to elicit target deadenylation.
Abstract: http://links.ealert.nature.com/ctt?kn=118&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=47&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Solution structures of the two PBZ domains from human APLF and their
interaction with poly(ADP-ribose) pp241 - 243
Sebastian Eustermann et al.
doi:10.1038/nsmb.1747
The solution structures of the two PAR-binding zinc finger (PBZ)
modules from APLF, a human protein putatively involved in DNA damage
response, are now presented. Together with binding studies with PAR
fragments and mutagenesis, the work sheds light on PAR recognition by
PBZ modules.
Abstract: http://links.ealert.nature.com/ctt?kn=121&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=62&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Nonsense-mediated mRNA decapping occurs on polyribosomes in
Saccharomyces cerevisiae pp244 - 247
Wenqian Hu, Christine Petzold, Jeff Coller and Kristian E Baker
doi:10.1038/nsmb.1734
Nonsense-mediated mRNA decay (NMD) recognizes and degrades mRNAs with
premature termination codons. In yeast, this occurs by decapping
followed by 5' to 3' exonucleolytic digestion. New work shows that
substrates of NMD pathway are targeted for decapping while the mRNA
is associated with polyribosomes. These findings are in contrast to
previous work which suggested that NMD occurs in ribosome-free P
bodies but are consistent with recent work showing that 'normal'
mRNAs are decapped co-translationally.
Abstract: http://links.ealert.nature.com/ctt?kn=114&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=73&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Structural basis of respiratory syncytial virus neutralization by
motavizumab pp248 - 250
Jason S McLellan et al.
doi:10.1038/nsmb.1723
Respiratory syncytial virus (RSV) is a highly contagious illness in
young children. The structure of antibody drug motavizumab in complex
with a 24-residue peptide corresponding to its epitope on RSV-fusion
glycoprotein suggests why it is more potent than its predecessor,
palivizumab (Synagis).
Abstract: http://links.ealert.nature.com/ctt?kn=115&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=80&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
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RESOURCE
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Schizosaccharomyces pombe genome-wide nucleosome mapping reveals
positioning mechanisms distinct from those of Saccharomyces cerevisiae
pp251 - 257
Alexandra B Lantermann et al.
doi:10.1038/nsmb.1741
Abstract: http://links.ealert.nature.com/ctt?kn=111&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=30&m=34602338&r=MTc2OTcxOTY5MQS2&b=2&j=NjY4MTEwODIS1&mt=1&rt=0
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