Article abstract
Nature Structural & Molecular Biology 15, 902 - 909 (2008)
Published online: 31 August 2008 | doi:10.1038/nsmb.1475
Primary microRNA transcripts are processed co-transcriptionally
Mariangela Morlando1,2, Monica Ballarino2,3, Natalia Gromak1,3, Francesca Pagano2, Irene Bozzoni2 & Nick J Proudfoot1
Abstract
microRNAs (miRNAs) are generated from long primary (pri-) RNA polymerase II (Pol II)–derived transcripts by two RNase III processing reactions: Drosha cleavage of nuclear pri-miRNAs and Dicer cleavage of cytoplasmic pre-miRNAs. Here we show that Drosha cleavage occurs during transcription acting on both independently transcribed and intron-encoded miRNAs. We also show that both 5'-3' and 3'-5' exonucleases associate with the sites where co-transcriptional Drosha cleavage occurs, promoting intron degradation before splicing. We finally demonstrate that miRNAs can also derive from 3` flanking transcripts of Pol II genes. Our results demonstrate that multiple miRNA-containing transcripts are co-transcriptionally cleaved during their synthesis and suggest that exonucleolytic degradation from Drosha cleavage sites in pre-mRNAs may influence the splicing and maturation of numerous mRNAs.
- Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
- Institute Pasteur Cenci-Bolognetti, Department of Genetics and Molecular Biology and IBPM, "La Sapienza", University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy.
- These authors contributed equally to this work.
Correspondence to: Nick J Proudfoot1 e-mail: nicholas.proudfoot@path.ox.ac.uk
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