January 2009 Volume 16 Number 1, pp 1 - 98
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EDITORIAL
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Evolving the discussion p1
As we enter 2009 and celebrate the anniversaries associated with
the birth of Darwin and publication of The Origin of Species, it's
worth asking why there isn't greater public awareness of the
increasing molecular evidence relevant to evolution and what can
be done to address this.
doi:10.1038/nsmb0109-1
http://www.nature.com/nsmb/journal/v16/n1/full/nsmb0109-1.html
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MEETING REPORT
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The Hsp90 mosaic: a picture emerges pp2 - 6
Hsp90s, molecular chaperones critically involved in many essential
cellular processes, were the focus of a recent international
conference held in Seeon, Germany. The scope of the conference
ranged from structural and mechanistic insights all the way to
medical applications.
Matthias P Mayer, Chrisostomos Prodromou and Judith Frydman
doi:10.1038/nsmb0109-2
http://www.nature.com/nsmb/journal/v16/n1/full/nsmb0109-2.html
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NEWS AND VIEWS
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Eye on RNA unwinding pp7 - 8
Biochemical studies on the spliceosomal helicase Brr2 reveal that
it is activated by Prp8, the master regulator of the splicing cycle.
Substitutions in Prp8 that cause retinal degeneration in humans
block activation of Brr2, providing insight into the molecular
pathology of retinitis pigmentosa.
David A Brow
doi:10.1038/nsmb0109-7
http://www.nature.com/nsmb/journal/v16/n1/full/nsmb0109-7.html
RNA stability: is it the endo' the world as we know it? pp9 - 10
Endonucleases have generally not been considered among the major
factors in well-studied mRNA-decay and quality-control pathways
in mammals and yeast. However, two important players in these
pathways, the exosome and SMG6, have now been shown to contain
functionally significant endonucleolytic activities.
Jeffrey Wilusz
doi:10.1038/nsmb0109-9
http://www.nature.com/nsmb/journal/v16/n1/full/nsmb0109-9.html
Chromodomain-mediated spreading on active genes pp11 - 13
The formation of heterochromatin involves spreading of repressor
proteins along large chromosomal domains. A new study reveals that
the concept of spreading also holds true for establishing domains
of active chromatin. More specifically, spreading of the Drosophila
melanogaster male-specific lethal (MSL) activator complex, which is
required for dosage compensation on the X chromosome, involves
interaction between the MSL3 chromodomain and histone H3 methylated
at lysine 36.
Alison M Hosey and Marjorie Brand
doi:10.1038/nsmb0109-11
http://www.nature.com/nsmb/journal/v16/n1/full/nsmb0109-11.html
Alternative splicing: regulation without regulators pp13 - 15
Alternative splicing is typically thought to be controlled by RNA
binding proteins that modulate the activity of the spliceosome. A
new study not only demonstrates that alternative splicing can be
regulated without the involvement of auxiliary splicing factors,
but also provides mechanistic insight into how this can occur.
Brenton R Graveley
doi:10.1038/nsmb0109-13
http://www.nature.com/nsmb/journal/v16/n1/full/nsmb0109-13.html
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RESEARCH HIGHLIGHTS
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Research highlights p16
doi:10.1038/nsmb0109-16
http://www.nature.com/nsmb/journal/v16/n1/full/nsmb0109-16.html
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ARTICLES
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Histone H3 tail clipping regulates gene expression pp17 - 22
Nucleosome stability can influence gene expression and is regulated
by nucleosome-positioning sequences, histone chaperones, remodeling
complexes, post-translational modifications and histone variants.
Now, histone H3 tail clipping has been added to the list. Kouzarides
and co-workers have identified a serine endopeptidase in yeast that
cleaves H3 after Ala21 and shows a preference for H3 tails with
repressive modifications. In vivo, this occurs at the promoters of
induced genes and precedes histone eviction when genes become fully
active.
Helena Santos-Rosa et al.
doi:10.1038/nsmb.1534
Abstract: http://links.ealert.nature.com/ctt?kn=4&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1534.html
miR-29 miRNAs activate p53 by targeting p85alpha and CDC42
pp23 - 29
The transcription factor and tumor suppressor p53 is central to many
stress responses and is the target of multiple regulators. The
regulatory subunit of PI3 kinase, p85alpha and CDC42 are now both
found to be targets of the miR-29 microRNAs. As p85alpha and CDC42
are repressors of p53, these miRNAs indirectly activate p53 and thus
apoptosis.
Seong-Yeon Park et al.
doi:10.1038/nsmb.1533
Abstract: http://links.ealert.nature.com/ctt?kn=100&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1533.html
High-resolution structure of the open NaK channel pp30 - 34
Channel gating in tetrameric cation channels occurs as structural
transitions that involve straightening and bending of inner helices
at a conserved glycine residue. Structural representatives of these
closed and opened states have come from crystal structure of KcsA
and MthK, respectively. The structure of NaK in the open state,
when combined with a previously determined structure of NaK in the
closed state, allows the detailed analysis of channel gating within
the same channel.
Amer Alam and Youxing Jiang
doi:10.1038/nsmb.1531
Abstract: http://links.ealert.nature.com/ctt?kn=81&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1531.html
Structural analysis of ion selectivity in the NaK channel
pp35 - 41
Ion selectivity is as important to ion channel function as channel
gating. Much of what is currently known about selectivity comes from
structural studies of K+-selective channels. Detailed structural
analysis of the ion binding sites in the NaK pore provides a first
look at the geometry and ionic selectivity in a Na+-permeable
channel and may provide a basis for understanding permeation through
nonselective cation channels.
Amer Alam and Youxing Jiang
doi:10.1038/nsmb.1537
Abstract: http://links.ealert.nature.com/ctt?kn=97&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1537.html
ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires
the C terminus of Prp8 pp42 - 48
Although a number of DExD/H-box family RNA-dependent ATPases are
required in the spliceosome, their regulation is unclear. The
Brr2-dependent unwinding of U4/U6 snRNAs, a key step in splicing,
is now shown to be promoted in a purified system by the C-terminal
region of Prp8, an enigmatic spliceosome component associated with
a dominant form of retinitis pigmentosa.
Corina Maeder, Alan K Kutach and Christine Guthrie
doi:10.1038/nsmb.1535
Abstract: http://links.ealert.nature.com/ctt?kn=39&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1535.html
SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells
pp49 - 55
Nonsense-mediated decay (NMD) is an mRNA surveillance process that
targets transcripts containing a premature stop codon for degradation.
Evidence now suggests that mammalian NMD involves an endonucleolytic
cleavage that is mediated by human SMG6.
Andrea B Eberle, Soren Lykke-Andersen, Oliver Muhlemann and Torben
Heick Jensen
doi:10.1038/nsmb.1530
Abstract: http://links.ealert.nature.com/ctt?kn=83&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1530.html
The exosome contains domains with specific endoribonuclease,
exoribonuclease and cytoplasmic mRNA decay activities pp56 - 62
The exosome is a large complex with cellular functions including
exoribonucleolytic mRNA degradation and processing of a number of
RNAs including small nuclear RNAs, small nucleolar RNAs and
ribosomal RNAs. The yeast exosome is now shown to possess an
unexpected endoribonucleolytic activity, and the essential Csl4
subunit is shown to contain a domain involved in mRNA decay. This
suggests that particular domains in the complex have specialized
roles.
Daneen Schaeffer et al.
doi:10.1038/nsmb.1528
Abstract: http://links.ealert.nature.com/ctt?kn=30&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1528.html
Rapid evolution of protein kinase PKR alters sensitivity to viral
inhibitors pp63 - 70
PKR responds to viral infection and shuts down translation through
phosphorylation of eIF2alpha. PKR is found to have rapidly evolved
in comparison to other kinases targeting the same substrate across a
broad range of vertebrate lineages. Some positively selected residues
are found to confer resistance to poxviral inhibitors that mimic
substrate. In addition, substituting a single residue in mouse PKR
with the corresponding residue under positive selection in human PKR
renders mouse PKR more resistant to K3L and vice versa, providing
evidence for species-specific selection driven by beneficial mutations.
Stefan Rothenburg et al.
doi:10.1038/nsmb.1529
Abstract: http://links.ealert.nature.com/ctt?kn=28&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1529.html
Inverse coupling in leak and voltage-activated K+ channel gates
underlies distinct roles in electrical signaling pp71 - 79
The negatively coupled movement of the activation and inactivation
gates of Kv channels regulates ion flow across membranes in response
to changes in membrane potential. Although they share a common pore
design, the K2P leak channels are open at all potentials and are
believed to act only through a slow inactivation gate. New data
reveal that, similarly to the Kv channels, leak channels possess a
constitutively open lower activation gate. Positive coupling between
the two gates ensure constant leak currents across the membrane.
Yuval Ben-Abu, Yufeng Zhou, Noam Zilberberg and Ofer Yifrach
doi:10.1038/nsmb.1525
Abstract: http://links.ealert.nature.com/ctt?kn=32&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1525.html
The mechanism of pentabromopseudilin inhibition of myosin motor
activity pp80 - 88
Myosins have roles in many biological processes that go beyond
muscle contraction and vesicle transport, including furrowing during
cytokinesis, signal transduction and RNA polymerase I-dependent
transcription. Studying these various complex processes will require
the use of isoform-specific small molecules that alter motor activity.
The marine natural product pentabromopseudilin is now shown to act
as an allosteric effector of myosin function and potent inhibitor of
vertebrate myosin-5a-dependent motor activity.
Roman Fedorov et al.
doi:10.1038/nsmb.1542
Abstract: http://links.ealert.nature.com/ctt?kn=43&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1542.html
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BRIEF COMMUNICATIONS
----------------------
Crystal structure of TIPE2 provides insights into immune homeostasis
pp89 - 90
TIPE2 is involved in immune homeostasis, and it has been assumed
that it contained a death effector domain (DED). Now the crystal
structure of TIPE2 reveals that it does not possess a DED, but
instead has a previously uncharacterized fold, with a large central
cavity that might accommodate a ligand.
Xu Zhang et al.
doi:10.1038/nsmb.1522
Abstract: http://links.ealert.nature.com/ctt?kn=41&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1522.html
An atypical RNA polymerase involved in RNA silencing shares small
subunits with RNA polymerase II pp91 - 93
Plants contain atypical RNA polymerases that have been implicated
in RNA silencing. An analysis of RNA polymerase V composition now
reveals that it unexpectedly shares some, but not all, subunits
found in RNA polymerase II, indicating that it may be a derived
version of this polymerase complex. Additional subunits are also
identified and implicated in RNA-mediated silencing.
Linfeng Huang et al.
doi:10.1038/nsmb.1539
Abstract: http://links.ealert.nature.com/ctt?kn=93&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1539.html
Structure of the motor subunit of type I restriction-modification
complex EcoR124I pp94 - 95
Type I restriction-modification enzymes recognize a target sequence
and translocate DNA from both sides while remaining stationary,
creating supercoiled loops and cleaving at nonspecific sites several
kilobases away. The crystal structure of the motor subunit of
EcoR124I is now solved, providing insight into these complex machines.
Mikalai Lapkouski et al.
doi:10.1038/nsmb.1523
Abstract: http://links.ealert.nature.com/ctt?kn=74&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1523.html
Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller
domain pp96 - 98
Sortilin is a neuronal receptor involved in sorting and signal
transduction. The crystal structure of the mature Sortilin ectodomain
bound to one of its ligands, neurotensin, reveals a binding tunnel
formed by the Sortilin beta-propeller domain. Combined with binding
and mutagenesis studies, the findings suggest that Sortilin substrates
compete for access to the tunnel so that only one ligand binds at a
time.
Esben M Quistgaard et al.
doi:10.1038/nsmb.1543
Abstract: http://links.ealert.nature.com/ctt?kn=2&m=30862867&r=MTU0OTA2NzU2NAS2&b=2&j=NDQ4NjQ4NDgS1&mt=1&rt=0
Article: http://www.nature.com/nsmb/journal/v16/n1/full/nsmb.1543.html
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