2026-04-27T07:46:31Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/78862024-11-29T13:42:40Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Mitxelena, Jone
author
Apraiz, Aintzane
author
Vallejo-Rodríguez, Jon
author
Malumbres Martinez, Marcos
author
Zubiaga, Ana M
funder
Ministerio de Ciencia e Innovación (España)
funder
Comunidad de Madrid (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Basque Government (España)
2019-07-10T11:14:00Z
2019-07-10T11:14:00Z
2016-03-09
Nucleic Acids Res. 2016 Mar 9. pii: gkw146.
0305-1048
http://hdl.handle.net/20.500.12105/7886
26961310
10.1093/nar/gkw146
1362-4962
Nucleic acids research
E2F transcription factors (E2F1-8) are known to coordinately regulate the expression of a plethora of target genes, including those coding for microRNAs (miRNAs), to control cell cycle progression. Recent work has described the atypical E2F factor E2F7 as a transcriptional repressor of cell cycle-related protein-coding genes. However, the contribution of E2F7 to miRNA gene expression during the cell cycle has not been defined. We have performed a genome-wide RNA sequencing analysis to identify E2F7-regulated miRNAs and show that E2F7 plays as a major role in the negative regulation of a set of miRNAs that promote cellular proliferation. We provide mechanistic evidence for an interplay between E2F7 and the canonical E2F factors E2F1-3 in the regulation of multiple miRNAs. We show that miR-25, -26a, -27b, -92a and -7 expression is controlled at the transcriptional level by the antagonistic activity of E2F7 and E2F1-3. By contrast, let-7 miRNA expression is controlled indirectly through a novel E2F/c-MYC/LIN28B axis, whereby E2F7 and E2F1-3 modulate c-MYC and LIN28B levels to impact let-7 miRNA processing and maturation. Taken together, our data uncover a new regulatory network involving transcriptional and post-transcriptional mechanisms controlled by E2F7 to restrain cell cycle progression through repression of proliferation-promoting miRNAs.
eng
E2F7 regulates transcription and maturation of multiple microRNAs to restrain cell proliferation
journal article
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URL
https://repisalud.isciii.es/bitstreams/b6898e40-31f5-4464-bda8-0284939eb572/download
File
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application/pdf
E2F7regulatestranscriptionandmaturation_2016.pdf
URL
https://repisalud.isciii.es/bitstreams/7e94ae14-3a70-4885-b269-bc8f6a8b3bc4/download
File
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text/plain
E2F7regulatestranscriptionandmaturation_2016.pdf.txt