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Cell. 2013 Dec 19;155(7):1568-80. doi: 10.1016/j.cell.2013.11.027.

Mammalian 5'-capped microRNA precursors that generate a single microRNA.

Author information

1
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
2
Department of Neurobiology, Kavli Institute of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
3
Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
4
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA. Electronic address: joan.steitz@yale.edu.

Abstract

MicroRNAs (miRNAs) are short RNA gene regulators typically produced from primary transcripts that are cleaved by the nuclear microprocessor complex, with the resulting precursor miRNA hairpins exported by exportin 5 and processed by cytoplasmic Dicer to yield two (5p and 3p) miRNAs. Here, we document microprocessor-independent 7-methylguanosine (m(7)G)-capped pre-miRNAs, whose 5' ends coincide with transcription start sites and 3' ends are most likely generated by transcription termination. By establishing a small RNA Cap-seq method that employs the cap-binding protein eIF4E, we identified a group of murine m(7)G-capped pre-miRNAs genome wide. The m(7)G-capped pre-miRNAs are exported via the PHAX-exportin 1 pathway. After Dicer cleavage, only the 3p-miRNA is efficiently loaded onto Argonaute to form a functional microRNP. This unusual miRNA biogenesis pathway, which differs in pre-miRNA synthesis, nuclear-cytoplasmic transport, and guide strand selection, enables the development of shRNA expression constructs that produce a single 3p-siRNA.

PMID:
24360278
PMCID:
PMC3899828
DOI:
10.1016/j.cell.2013.11.027
[Indexed for MEDLINE]
Free PMC Article

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