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1:10-1:15 Chairperson’s Opening Remarks
1:15-1:45 miRNAs and HIV Infection
Lars Aagaard, Ph.D., Division of Molecular Biology, Beckman Research Inst. of the City of Hope
We have been investigating the profile of endogenous miRNA expression following HIV-1 infection of T-lymphocytes. One particular microRNA is routinely elevated following infection. In order to investigate the functional consequences of this upregulation, cellular targets for this have been identified and tested. In addition to the endogenous miRNA, we have strong data supporting the functional role HIV encoded TAR as a miRNA. The potential target for TAR has been identified and tested as well. This talk will focus on the target and its role in HIV infection.
1:45-2:15 microRNAs Targeting Genomic Repeat Elements Within mRNAs
Neil Smalheiser, M.D., Ph.D., Assistant Professor, Psychiatry, University of Illinois, Chicago
Recently, we reported that four microRNAs show perfect complementarity with MIR/LINE-2 elements within human mRNAs. This finding raises the question of whether microRNAs might also target other genomic repeats and transposable elements. Here, we demonstrate that almost 30 human microRNAs exhibit typical short-seed complementarity with a specific site within Alu elements that is highly conserved within 3' untranslated regions of human mRNAs. The results suggest that at least some Alu elements within human mRNAs serve as microRNA targets.
2:15-2:45 microRNA Regulatory Strategies of Human Cellular Networks
Edwin Wang, Ph.D., Scientist, Biotechnology Research Institute, National Research Council Canada
According to the dogma of molecular biology, RNAs are passive messengers and take charge of transferring genetic information only. However, the dogma has been challenged by the recent findings that microRNA (miRNA) is able to negatively regulate genes. It is estimated that 10%-30% of genes might be regulated by miRNAs. The diversity and abundance of miRNA targets offer an enormous level of combinatorial possibilities and suggest that miRNAs and their targets appear to form a complex regulatory network intertwined with other cellular networks. However, it is unclear if and how miRNAs might orchestrate their regulation of cellular networks and how regulation of these networks might contribute to the biological functions of miRNAs. Here we address these questions by analyzing the interactions between miRNAs and human cellular networks including signaling, metabolic and gene regulatory networks. We uncovered that in signaling networks, miRNAs predominantly target positive regulatory motifs, highly connected scaffolds and most downstream network components, but less frequently target negative regulatory motifs, common components of basic cellular machines and most upstream network components. In addition, when an adaptor has potential to recruit more downstream components, these components are more frequently targeted by miRNAs. These results imply that miRNAs have potential functions in facilitating robust transitions of cellular response to extracellular signals and maintaining cellular homeostasis. We also uncovered that through preferentially targeting the network nodes with distinct network structural features, microRNA regulates metabolic networks globally, regionally and locally to reduce or block specific metabolite production in a way of fine-tuning or directly blocking metabolic flows. This work uncovers the principles of miRNA regulation of cellular networks and generates a set of testable hypotheses.
2:45-3:30 Refreshment Break with Exhibit and Poster Viewing
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3:30-3:50 Microrna
Profiling Of Breast Cancer Using A Novel Locked Nucleic Acid (LNA) Based
Microarray
Soren Moller, Ph.D, CSO, VP R&D, Exiqon A/S
To identify new biomarkers for breast cancer we studied the global
expression of miRNAs in tumor and normal adjacent tissue. Using a
microarray platform with LNA-modified capture probes we found numerous
differentially expressed miRNAs, including those previously reported to be
associated with breast cancer. The results were confirmed using miRCURY
LNA qPCR. Further, we identified several novel miRNA candidates by
454-sequencing, some of which could have diagnostic and prognostic
potential for breast cancer patients. |
Sponsored by
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3:50 Unravelling the Mystery of miRNA Targets
Vera Atzorn, Ph.D., Actigenics Marketing and Communication Manager,
Cepheid
Even though microRNAs have been proven essential, their complete functional assessment remains a difficult task. This is mainly due to their molecular mode of action, which allows a single microRNA to impact the translation of hundreds of mRNAs. However, this apparent complexity refers to well defined interaction networks in which subgroups of microRNA regulate conjointly specific cellular events.miRgate, our all-in-one software solution, integrates network information regarding microRNAs and provides excellent filters to significantly enhance knowledge on real microRNA function.
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4:10 High
Throughput microRNA Expression Profiling Using a Bead Based Multiplex
System
Dr. Keld Sorensen, Director, R&D, Luminex Corporation
The combination of two technologies, namely the Locked Nucleic Acid (LNA
) and the bead based multiplexing (xMAP?), allows the design of miRNA
assays that are both flexible and very specific. In brief, the assay
consists of direct biotinylation of the 3' end of a sample of total RNA,
followed by capture on LNA probes on the xMAP beads. The assays allow
users up to 100 different capture probes in a singlemicrotiter well. With
a total assay time of only a few hours, and the high level of
multiplexing, the FlexmiR kits yield a throughput of thousands of data
points per working day. Incorporating LNA technology within
theoligonucleotide capture probes greatly increases the affinity of the
probes fortheir complementary mature miRNA targets leading to significant
increases anduniformity of assay specificity including single base
discrimination of closely related miRNAs.
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