It is increasingly clear that the biological functions of a transcription factor cannot be fully understood solely on the basis of protein-coding genes that fall under its control. Many transcription factors regulate expression of miRNAs, which affect the cell by modulating translation and stability of mRNAs. The identities and the roles of NF-κB-regulated miRNAs have been attracting research interest for a long time. We revisited this issue in a system with controlled expression of one of the key regulators of NF-κB, RIPK1. Several regulated miRNAs were identified, including miR-146a, miR-215 and miR-497. The miRNAs were also inducible by IL-1β, but not when NF-κB activity was repressed by mutant IκBα. The presence of a miR-497 site was predicted in the 3′-UTR of IKBKB gene, which encodes IKKβ. Using appropriately engineered reporters, we confirmed that this site can be a target of suppressive action of miR-497. Our findings suggest that NF-κB controls expression of a miRNA, which may reduce production of IKKβ. Considering the role of IKKβ in the canonical pathway of NF-κB activation, our observations may indicate a new mechanism that modulates the magnitude of such activation, as well as the propensity of a cell to engage canonical vs. non-canonical pathways.
MicroRNAs are short RNA molecules that regulate function and stability of a large subset of eukaryotic mRNAs. In the main pathway of microRNA biogenesis, a short "hairpin" is excised from a primary transcript by ribonuclease DROSHA, followed by additional nucleolytic processing by DICER and inclusion of the mature microRNA into the RNA-induced silencing complex. We report that a microRNA-like molecule is encoded by human DROSHA gene within a predicted stem-loop element of the respective transcript. This putative mature microRNA is complementary to DROSHA transcript variant 1 and can attenuate expression of the corresponding protein. The findings suggest a possibility for a negative feedback loop, wherein DROSHA processes its own transcript and produces an inhibitor of its own biosynthesis.
In Österreich wird Computermusik an allen drei iVlusikhochschulen unterrichtet, und zwar an folgenden Instituten: an der Musikhochschule Wien am Institut für Elektroakustik und experimentelle Musik (Leiter: o. Prof. Roman Haubenstock-Ramati, Mitarbeiter: Hellmut Gottwald, Dieter Kaufmann, Peter Mechtler), an der Musikhochschule "Mozarteum" Salzburg am Institut für elektronische Musik (Leiter: o. Prof. Gerhard Wimberger, Mitarbeiter: Klaus Ager, Irmfried Radauer) und an der Musikhochschule Graz am Institut für elektronische Musik (Leiter: o. Prof. Dipl.-Ing. Heinz Honig, Mitarbeiter: Helmut Dencker, Herbert Huber, John Simonson). Der Verfasser dieses Beitrags ist Lehrbeauftragter am Wiener Institut für Elektroakustik (Vorlesung "Music processing") und außerdem mit der Neueinrichtung des Instituts befaßt, das in die Rienößigasse 12 übersiedelt und dort im November neueröffnet wird.
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