Feed-forward microprocessing and splicing activities at a microRNA-containing intron

Maja M. Janas, Mehdi Khaled, Steffen Schubert, Jacob G. Bernstein, David Golan, Rosa A. Veguilla, David E. Fisher, Noam Shomron, Carmit Levy*, Carl D. Novina

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The majority of mammalian microRNA (miRNA) genes reside within introns of protein-encoding and non-coding genes, yet the mechanisms coordinating primary transcript processing into both mature miRNA and spliced mRNA are poorly understood. Analysis of melanoma invasion suppressor miR-211 expressed from intron 6 of melastatin revealed that microprocessing of miR-211 promotes splicing of the exon 6-exon 7 junction of melastatin by a mechanism requiring the RNase III activity of Drosha. Additionally, mutations in the 5′ splice site (5′SS), but not in the 3′SS, branch point, or polypyrimidine tract of intron 6 reduced miR-211 biogenesis and Drosha recruitment to intron 6, indicating that 5′SS recognition by the spliceosome promotes microprocessing of miR-211. Globally, knockdown of U1 splicing factors reduced intronic miRNA expression. Our data demonstrate novel mutually-cooperative microprocessing and splicing activities at an intronic miRNA locus and suggest that the initiation of spliceosome assembly may promote microprocessing of intronic miRNAs.

Original languageEnglish
Article numbere1002330
JournalPLoS Genetics
Volume7
Issue number10
DOIs
StatePublished - Oct 2011

Funding

FundersFunder number
National Institute of Arthritis and Musculoskeletal and Skin DiseasesR01AR043369

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