title: Extensive variation in the 5'-UTR of Dicer mRNAs influences translational efficiency.
abstract: The Dicer enzyme is a key component of the RNA interference pathway and also responsible for the processing of micro RNAs, non-coding RNA molecules which regulate the activity of mRNAs by antisense base pairing. Little is known about the structure and regulation of human Dicer mRNA. A comprehensive characterization of Dicer 5'-untranslated region (5'-UTR) RNA structure revealed important diversity within human Dicer mRNA transcripts. Three exon 1 variants were defined, some of which exhibited very restricted patterns of tissue distribution. A number of alternatively spliced 5'-leader exons were also noted, revealing the potential for complex post-transcriptional regulation. Surprisingly, this diversity all occurred within the 5'-UTR of Dicer mRNAs and did not affect the coding region. The Dicer mRNA 5'-UTR variants had profound effects on translational efficiency both in vitro and in transiently transfected cells. A number of major Dicer RNA species are inefficient substrates for the translational machinery.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ont., Canada.
authors.forename: Sundeep
authors.initials: S
authors.lastname: Singh
authors.forename: Sian C
authors.initials: SC
authors.lastname: Bevan
authors.forename: Kedar
authors.initials: K
authors.lastname: Patil
authors.forename: Derek C
authors.initials: DC
authors.lastname: Newton
authors.forename: Philip A
authors.initials: PA
authors.lastname: Marsden
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D003001:Cloning, Molecular; D005091:Exons; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D012333:RNA, Messenger; D043244:Ribonuclease III