dictyNews
Electronic Edition
Volume 42, number 21
September 9, 2016
Please submit abstracts of your papers as soon as they have been
accepted for publication by sending them to [log in to unmask]
or by using the form at
http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit.
Back issues of dictyNews, the Dicty Reference database and other
useful information is available at dictyBase - http://dictybase.org.
Follow dictyBase on twitter:
http://twitter.com/dictybase
=========
Abstracts
=========
Convergent evolution of tRNA gene targeting preferences in compact
genomes
Thomas Spaller1, Eva Kling1, Gernot Glφckner2,3, Falk Hillmann4,
Thomas Winckler1
1 Institute of Pharmacy, Department of Pharmaceutical Biology,
Friedrich Schiller University Jena, Germany
2 Institute for Biochemistry I, Medical Faculty, University of
Cologne, Germany
3 Institute for Freshwater Ecology and Inland Fisheries, IGB,
Berlin, Germany
4 Junior Research Group Evolution of Microbial Interaction,
Leibniz Institute for Natural Product Research and Infection
Biology - Hans Knφll Institute, Jena, Germany
Mobile DNA, in press
Background: In gene-dense genomes, mobile elements are confronted
with highly selective pressure to amplify without causing excessive
damage to the host. The targeting of tRNA genes as potentially safe
integration sites has been developed by retrotransposons in various
organisms such as the social amoeba Dictyostelium discoideum and
the yeast Saccharomyces cerevisiae. In D. discoideum, tRNA gene-
targeting retrotransposons have expanded to approximately 3% of the
genome. Recently obtained genome sequences of species representing
the evolutionary history of social amoebae enabled us to determine
whether the targeting of tRNA genes is a generally successful strategy
for mobile elements to colonize compact genomes.
Results: During the evolution of dictyostelids, different retrotransposon
types independently developed the targeting of tRNA genes at least six
times. DGLT-A elements are long terminal repeat (LTR) retrotransposons
that display integration preferences ~15 bp upstream of tRNA gene-coding
regions reminiscent of the yeast Ty3 element. Skipper elements are
chromoviruses that have developed two subgroups: one has canonical
chromo domains that may favor integration in centromeric regions,
whereas the other has diverged chromo domains and is found ~100 bp
downstream of tRNA genes. The integration of D. discoideum non-LTR
retrotransposons ~50 bp upstream (TRE5 elements) and ~100 bp
downstream (TRE3 elements) of tRNA genes, respectively, likely emerged
at the root of dictyostelid evolution. We identified two novel non-LTR
retrotransposons unrelated to TREs: one with a TRE5-like integration
behavior and the other with preference ~4 bp upstream of tRNA genes.
Conclusions: Dictyostelid retrotransposons demonstrate convergent
evolution of tRNA gene targeting as a probable means to colonize the
compact genomes of their hosts without being excessively mutagenic.
However, high copy numbers of tRNA gene-associated retrotransposons,
such as those observed in D. discoideum, are an exception, suggesting
that the targeting of tRNA genes does not necessarily favor the
amplification of position-specific integrating elements to high copy
numbers under the repressive conditions that prevail in most host cells.
submitted by: Thomas Winckler [[log in to unmask]]
Identification of brefelamide as a novel inhibitor of osteopontin
that suppresses invasion of A549 lung cancer cells
Jing Zhang, Osamu Yamada, Shinya Kida, Yoshihisa Matsushita,
Shinya Murase, Toshio Hattori, Yuzuru Kubohara, Haruhisa Kikuchi
and Yoshiteru Oshima
Oncol. REP. 36: 2357-2364, 2016
The contribution of aberrant osteopontin (OPN) expression to tumor
progression and metastasis has been documented in a wide spectrum
of malignancies, and targeted inhibition of OPN has therefore emerged
as an attractive strategy for cancer therapy. Transcription of OPN
is regulated by various transcription factors, and our recently published
study demonstrated that downregulation of OPN is an important event
in the TGF-beta cytostatic program. We report here that brefelamide,
isolated from Dictyostelium brefeldianum, exerts an inhibitory effect on
OPN expression and function in A549 human lung carcinoma cells. The
promoter, RNA, and protein levels of OPN were decreased in
brefelamide-treated A549 cells, which was accompanied by reduced
invasive ability in vitro. OPN inhibition by brefelamide was largely
abrogated by disruption of a putative TGF-beta inhibitory element in the
OPN promoter. Treatment with brefelamide induced Smad4 expression,
and knockdown of Smad4 by RNA interference partially diminished the
inhibitory effect of brefelamide on OPN. These results indicate that
brefelamide inhibited OPN-mediated cell invasion through restoration of
the OPN repression by TGF-beta /Smad signaling. Together with the
reported antiproliferative property, our findings suggest that brefelamide
might serve as a potential candidate for the development of a new
antitumor and antimetastatic agent.
submitted by: Haruhisa Kikuchi [[log in to unmask]]
Aberrant adhesion impacts early development in a Dictyostelium model
for juvenile neuronal ceroid lipofuscinosis
Robert J. Huber1*, Michael A. Myre2 and Susan L. Cotman3
1Department of Biology, Trent University, Peterborough, Ontario, Canada
2Department of Biological Sciences, University of Massachusetts Lowell,
Lowell, Massachusetts, USA
3Center for Human Genetic Research, Massachusetts General Hospital,
Harvard Medical School, Boston, Massachusetts, USA
These authors contributed equally
*Corresponding author
Cell Adhesion & Migration, in press
Neuronal ceroid lipofuscinosis (NCL), also known as Batten disease,
refers to a group of severe neurodegenerative disorders that primarily
affect children. The most common subtype of the disease is caused by
loss-of-function mutations in CLN3, which is conserved across model
species from yeast to human. The precise function of the CLN3 protein
is not known, which has made targeted therapy development challenging.
In the social amoeba Dictyostelium discoideum, loss of Cln3 causes
aberrant mid-to-late stage multicellular development. In this study,
we show that Cln3-deficiency causes aberrant adhesion and aggregation
during the early stages of Dictyostelium development. cln3- cells form
~30% more multicellular aggregates that are comparatively smaller than
those formed by wild-type cells. Loss of Cln3 delays aggregation, but
has no significant effect on cell speed or cAMP-mediated chemotaxis.
The aberrant aggregation of cln3- cells cannot be corrected by manual
pulsing cells with cAMP. Moreover, there are no significant differences
between wild-type and cln3- cells in the expression of genes linked to
cAMP chemotaxis (e.g., adenylyl cyclase, acaA; the cAMP receptor, carA;
cAMP phosphodiesterase, pdsA; g-protein alpha 9 subunit, gpaI). However,
during this time in development, cln3- cells show reduced cell-substrate
and cell-cell adhesion, which correlate with changes in the levels of the
cell adhesion proteins CadA and CsaA. Specifically, loss of Cln3
decreases the intracellular level of CsaA and increases the amount of
soluble CadA in conditioned media. Together, these results suggest that
the aberrant aggregation of cln3- cells is due to reduced adhesion during
the early stages of development. Revealing the molecular basis underlying
this phenotype may provide fresh new insight into CLN3 function.
submitted by: Robert Huber [[log in to unmask]]
==============================================================
[End dictyNews, volume 42, number 21]
|
