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Int. J. Mol. Sci. 2015, 16(4), 8110-8127; doi:10.3390/ijms16048110

Sequence Features of Drosha and Dicer Cleavage Sites Affect the Complexity of IsomiRs

Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14 Str., 61-704 Poznan, Poland
These authors contributed equally to this work.
Present address: Faculty of Life Sciences, University of Manchester, M13 9PT Manchester, UK.
*
Author to whom correspondence should be addressed.
Academic Editor: Michael R. Ladomery
Received: 10 February 2015 / Revised: 25 March 2015 / Accepted: 27 March 2015 / Published: 10 April 2015
(This article belongs to the Special Issue RNA Interference)
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Abstract

The deep-sequencing of small RNAs has revealed that different numbers and proportions of miRNA variants called isomiRs are formed from single miRNA genes and that this effect is attributable mainly to imprecise cleavage by Drosha and Dicer. Factors that influence the degree of cleavage precision of Drosha and Dicer are under investigation, and their identification may improve our understanding of the mechanisms by which cells modulate the regulatory potential of miRNAs. In this study, we focused on the sequences and structural determinants of Drosha and Dicer cleavage sites, which may explain the generation of homogeneous miRNAs (in which a single isomiR strongly predominates) as well as the generation of heterogeneous miRNAs. Using deep-sequencing data for small RNAs, we demonstrate that the generation of homogeneous miRNAs requires more sequence constraints at the cleavage sites than the formation of heterogeneous miRNAs. Additionally, our results indicate that specific Drosha cleavage sites have more sequence determinants in miRNA precursors than specific cleavage sites for Dicer and that secondary structural motifs in the miRNA precursors influence the precision of Dicer cleavage. Together, we present the sequence and structural features of Drosha and Dicer cleavage sites that influence the heterogeneity of the released miRNAs. View Full-Text
Keywords: miRNA precursor sequence; miRNA precursor structure; heterogeneity; homogeneity; Dicer; Drosha miRNA precursor sequence; miRNA precursor structure; heterogeneity; homogeneity; Dicer; Drosha
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Starega-Roslan, J.; Witkos, T.M.; Galka-Marciniak, P.; Krzyzosiak, W.J. Sequence Features of Drosha and Dicer Cleavage Sites Affect the Complexity of IsomiRs. Int. J. Mol. Sci. 2015, 16, 8110-8127.

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