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1.
RNA Biol ; 14(11): 1508-1513, 2017 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-28665784

RESUMEN

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.


Asunto(s)
ARN Helicasas DEAD-box/genética , MicroARNs/genética , Procesamiento Postranscripcional del ARN , ARN Mensajero/genética , Complejo Silenciador Inducido por ARN/genética , Ribonucleasa III/genética , Emparejamiento Base , Secuencia de Bases , Línea Celular Transformada , ARN Helicasas DEAD-box/metabolismo , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Células HEK293 , Humanos , MicroARNs/metabolismo , Conformación de Ácido Nucleico , ARN Mensajero/metabolismo , Complejo Silenciador Inducido por ARN/metabolismo , Ribonucleasa III/metabolismo
2.
Oncotarget ; 6(19): 17097-106, 2015 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-26020802

RESUMEN

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-1ß, 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 IKKß. 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 IKKß. Considering the role of IKKß 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.


Asunto(s)
Regulación de la Expresión Génica/fisiología , MicroARNs/metabolismo , FN-kappa B/biosíntesis , Transducción de Señal/fisiología , Línea Celular , Retroalimentación Fisiológica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Quinasa I-kappa B/biosíntesis , Immunoblotting , Reacción en Cadena de la Polimerasa , Regulación hacia Arriba
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