Extensive variation in the 5′-UTR of Dicer mRNAs influences translational efficiency

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ont., Canada.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 10/2005; 335(3):643-50. DOI: 10.1016/j.bbrc.2005.07.138
Source: PubMed


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.

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    • "Like Drosha, Dicer contains associated proteins TRBP, PACT which increases Dicer stability and activity. There are various isoforms of Dicer and the roles of these isoforms are not known [83, 84]. The mature miRNA then associates with a protein complex known as RNA induced silencing complex (RISC) at 3′UTR or 5′UTR or in ORF of target genes [10] (Figure 1). "
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    • "Further, various 5′-UTRs with different cis RNA regulatory elements can be produced via alternative splicing. The ATG start codon is localized in exon 2 [18]. To date, four mRNA variants encoding full-length Dicer enzymes have been identified (∶95552565–95624347;t = ENST00000393063). "
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    • "Pre-miRNAs are exported to the cytoplasm where the endoribonuclease, Dicer, processes them into mature miRNAs. These mature molecules are subsequently integrated into the RNA-induced silencing complex (RISC), the functional unit of which inhibits mRNA translation [11] [12]. "
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