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

PLoS Genet

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

Published: October 2011

AI Article Synopsis

  • The study focuses on how microRNA (miRNA) genes, particularly miR-211, are processed from introns of larger genes and how this process affects gene splicing.
  • Key findings show that the RNase III enzyme Drosha is crucial for both the formation of mature miR-211 and for facilitating the splicing of associated exons in the melastatin gene.
  • Mutations in specific splice sites highlighted a connection between spliceosome assembly and miRNA biogenesis, indicating that splicing factors influence the expression of intronic miRNAs.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197686PMC
http://dx.doi.org/10.1371/journal.pgen.1002330DOI Listing

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