| Speaker: |
Stefan A. Muljo
National Institutes of Health, Bethesda, Maryland, USA |
| Title: |
Dissecting microRNA function using mouse genetics and genomics |
| abstract : | In order to elucidate the impact of a microRNA on gene expression programs,
we perform deep sequencing of RNA (RNA-seq), and compare the transcriptome
of miRNA-deficient cells to wild type controls. Computational analyses
allow us to detect specific gene expression signatures imposed by the miRNA.
I will illustrate using miR-155 as an example. This strategy uncovered a
polycomb group protein as a direct miRNA target and its hitherto unsuspected
role in regulating cytokine gene transcription.
In a second story, we consider Lin28 as a reprogramming factor. One well
known function of Lin28 is to bind the let-7 family of miRNAs and inhibit
their processing into mature miRNAs by targeting the precursors for
uridylation and degradation. Interestingly, Lin28a is highly expressed in
embryonic stem cells and not detectable in adult tissues. Conversely, let-7
is not detectable in embryonic stem cells and expressed upon
differentiation. Furthermore, a paralog, Lin28b, is highly expressed during
fetal hematopoiesis but not during adult hematopoiesis. I will discuss our
latest understanding of Lin28 and let-7 function.
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