Extensive variation in the 5′-UTR of Dicer mRNAs influences translational efficiency
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.
Available from: Ram Babu Undi
- "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  (Figure 1). "
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ABSTRACT: The production of different types of blood cells including their formation, development, and differentiation is collectively known as haematopoiesis. Blood cells are divided into three lineages erythriod (erythrocytes), lymphoid (B and T cells), and myeloid (granulocytes, megakaryocytes, and macrophages). Haematopoiesis is a complex process regulated by several mechanisms including microRNAs (miRNAs). miRNAs are small RNAs which regulate the expression of a number of genes involved in commitment and differentiation of hematopoietic stem cells. Evidence shows that miRNAs play an important role in haematopoiesis; for example, myeloid and erythroid differentiation is blocked by the overexpression of miR-15a. miR-221, miR-222, and miR-24 inhibit the erythropoiesis, whereas miR-150 plays a role in B and T cell differentiation. miR-146 and miR-10a are downregulated in megakaryopoiesis. Aberrant expression of miRNAs was observed in hematological malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myelomas, and B cell lymphomas. In this review we have focused on discussing the role of miRNA in haematopoiesis.
Advances in Hematology 12/2013; 2013(8):695754. DOI:10.1155/2013/695754
Available from: Agata Tyczewska
- "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 . To date, four mRNA variants encoding full-length Dicer enzymes have been identified (http://www.ensembl.org/Homo_sapiens/Transcript/Summary?db=coreg=ENSG00000100697r=14∶95552565–95624347;t = ENST00000393063). "
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ABSTRACT: The precise regulation of microRNA (miRNA) biogenesis seems to be critically important for the proper functioning of all eukaryotic organisms. Even small changes in the levels of specific miRNAs can initiate pathological processes, including carcinogenesis. Accordingly, there is a great need to develop effective methods for the regulation of miRNA biogenesis and activity. In this study, we focused on the final step of miRNA biogenesis; i.e., miRNA processing by Dicer. To test our hypothesis that RNA molecules can function not only as Dicer substrates but also as Dicer regulators, we previously identified by SELEX a pool of RNA oligomers that bind to human Dicer. We found that certain of these RNA oligomers could selectively inhibit the formation of specific miRNAs. Here, we show that these specific inhibitors can simultaneously bind both Dicer and pre-miRNAs. These bifunctional riboregulators interfere with miRNA maturation by affecting pre-miRNA structure and sequestering Dicer. Based on these observations, we designed a set of short oligomers (12 nucleotides long) that were capable of influencing pre-miRNA processing in vitro, both in reactions involving recombinant human Dicer and in cytosolic extracts. We propose that the same strategy may be used to develop effective and selective regulators to control the production of any miRNA. Overall, our findings indicate that the interactions between pre-miRNAs and other RNAs may form very complex regulatory networks that modulate miRNA biogenesis and consequently gene expression.
PLoS ONE 10/2013; 8(10):e77703. DOI:10.1371/journal.pone.0077703 · 3.23 Impact Factor
Available from: Rhonda K Yantiss
- "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  . "
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ABSTRACT: MicroRNAs (miRNAs) comprise a recently discovered class of small, 18-25 nucleotide, noncoding RNA sequences that regulate gene expression at the posttranscriptional level by binding to and inhibiting the translation of target messenger RNAs (mRNAs). Characteristic patterns of miRNA expression have been described in several malignancies of the gastrointestinal tract, and numerous investigators have demonstrated interactions between specific miRNA species and target oncogenes or tumor-suppressor genes. It is clear that miRNAs play an important role in regulating expression of a number of genes involved in gastrointestinal carcinogenesis, and, thus, these molecules may represent either diagnostic markers of, or therapeutic targets for, some types of malignancy. This paper summarizes the literature regarding miRNA expression in carcinomas of the colon, pancreas, and liver and discusses some of the mechanisms by which these molecules participate in gastrointestinal oncogenesis.
Pathology Research International 02/2011; 2011(5):124608. DOI:10.4061/2011/124608
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