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Quelle: Hammond 2005 Seite(n): 5824, Zeilen: r.col: 20ff |
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[Drosha is a Class II enzyme. This enzyme assumes a pseudo-dimer catalytic] core similar to Dicer (Han et al, 2004). The substrates of Drosha, miRNA primary transcripts, are structurally distinct from Dicer substrates. Drosha does not process from a dsRNA terminus. Rather, data suggests that primarily the stemloop structure is recognized. In particular, the loop size appears to be important for recognition (Zeng et al, 2005). In addition, unstructured sequences flanking the stemloop are essential for processing (Chen et al, 2004; Zeng et al, 2005). It is not evident how Drosha is able to recognize these sequences, as they are outside of the dsRNA stem. Possibly other unidentified cofactors play a role. Conserved sequence elements have been found in flanking regions of C. elegans miRNAs (Ohler et al, 2004). | Drosha is a Class II enzyme as shown in Fig. 1. This enzyme assumes a pseudo-dimer catalytic core similar to Dicer [27]. The substrate of Drosha, microRNA primary transcripts, is structurally distinct from Dicer substrates. Drosha does not process from a dsRNA terminus. Rather, data suggests that the stem–loop structure is recognized. In particular, the loop size appears to be important for recognition [28]. In addition, unstructured sequences flanking the stem–loop are essential for processing [29,30]. It is not evident how Drosha would recognize these sequences, as they are outside of the dsRNA stem. Possibly other, unidentified cofactors play a role. Conserved sequence elements have been found in flanking regions of C. elegans microRNAs [31].
[27] Han, J., Lee, Y., Yeom, K.H., Kim, Y.K., Jin, H. and Kim, V.N. (2004) The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 18, 3016–3027. [28] Zeng, Y., Yi, R. and Cullen, B.R. (2005) Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J. 24, 138–148. [29] Chen, C.Z., Li, L., Lodish, H.F. and Bartel, D.P. (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303, 83–86. [30] Zeng, Y. and Cullen, B.R. (2005) Efficient processing of primary microRNA hairpins by Drosha requires flanking non-structured RNA sequences. J. Biol. Chem.. [31] Ohler, U., Yekta, S., Lim, L.P., Bartel, D.P. and Burge, C.B. (2004) Patterns of flanking sequence conservation and a characteristic upstream motif for microRNA gene identification. RNA 10, 1309–1322 |
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