The muscle-specific long noncoding RNA linc-MD1 was shown to be expressed during early phases of muscle differentiation and to trigger the switch to later stages by acting as a sponge for miR-133 and nniR-135. Notably, linc-MD1 is also the host transcript of miR-133b, and their biogenesis is mutually exclusive. Here, we describe that this alternative synthesis is controlled by the HuR protein, which favors linc-MD1 accumulation through its ability to bind linc-MD1 and repress Drosha cleavage. We show that HuR is under the repressive control of miR-133 and that the sponging activity of linc-MD1 consolidates HuR expression in a feedforward positive loop. Finally, we show that HuR also acts in the cytoplasm, reinforcing linc-MD1 sponge activity by cooperating for miRNA recruitment. An increase in nniR-133 synthesis, mainly from the two unrelated miR-133a coding genomic loci, is likely to trigger the exit from this circuitry and progression to later differentiation stages.

A Feedforward Regulatory Loop between HuR and the Long Noncoding RNA linc-MD1 Controls Early Phases of Myogenesis / Legnini, Ivano; Morlando, Mariangela; Mangiavacchi, Arianna; Fatica, Alessandro; Bozzoni, Irene. - In: MOLECULAR CELL. - ISSN 1097-2765. - STAMPA. - 53:3(2014), pp. 506-514. [10.1016/j.molcel.2013.12.012]

A Feedforward Regulatory Loop between HuR and the Long Noncoding RNA linc-MD1 Controls Early Phases of Myogenesis

LEGNINI, IVANO;MORLANDO, MARIANGELA;MANGIAVACCHI, ARIANNA;FATICA, Alessandro;BOZZONI, Irene
2014

Abstract

The muscle-specific long noncoding RNA linc-MD1 was shown to be expressed during early phases of muscle differentiation and to trigger the switch to later stages by acting as a sponge for miR-133 and nniR-135. Notably, linc-MD1 is also the host transcript of miR-133b, and their biogenesis is mutually exclusive. Here, we describe that this alternative synthesis is controlled by the HuR protein, which favors linc-MD1 accumulation through its ability to bind linc-MD1 and repress Drosha cleavage. We show that HuR is under the repressive control of miR-133 and that the sponging activity of linc-MD1 consolidates HuR expression in a feedforward positive loop. Finally, we show that HuR also acts in the cytoplasm, reinforcing linc-MD1 sponge activity by cooperating for miRNA recruitment. An increase in nniR-133 synthesis, mainly from the two unrelated miR-133a coding genomic loci, is likely to trigger the exit from this circuitry and progression to later differentiation stages.
2014
hur; long non coding rna; micro rna
01 Pubblicazione su rivista::01a Articolo in rivista
A Feedforward Regulatory Loop between HuR and the Long Noncoding RNA linc-MD1 Controls Early Phases of Myogenesis / Legnini, Ivano; Morlando, Mariangela; Mangiavacchi, Arianna; Fatica, Alessandro; Bozzoni, Irene. - In: MOLECULAR CELL. - ISSN 1097-2765. - STAMPA. - 53:3(2014), pp. 506-514. [10.1016/j.molcel.2013.12.012]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/540146
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