Abstract
Traditionally, researchers match a microRNA guide strand to mRNA sequences using sequence comparisons to predict its potential target genes. However, many of the predictions can be false positives due to limitations in sequence comparison alone. In this work, we consider the association of two related RNA structures that share a common guide strand: the microRNA duplex and the microRNA-target binding structure. We have analyzed thousands of such structure pairs and found many of them share high structural similarity. Therefore, we conclude that when predicting microRNA target genes, considering just the microRNA guide strand matches to gene sequences may not be sufficient — The microRNA duplex structure formed by the guide strand and its companion passenger strand must also be considered. We have developed software to translate RNA binding structure into encoded representations, and we have also created novel automatic comparison methods utilizing such encoded representations to determine RNA structure similarity. Our software and methods can be utilized in the other RNA secondary structure comparisons as well.
Highlights
MicroRNAs are small noncoding RNAs about 21 nucleotides in length that regulate gene expressions. miRNAs target messenger RNAs and trigger either their translational repression or degradation [1,2,3,4]
The traditional understanding about miRNA is that the passenger strand is excluded during duplex unwinding and only the guide strand is needed to guide the activated RNA-Induced Silencing Complex (RISC) to target messenger RNAs (mRNAs); the passenger strand does not seem to play any role in the targeting process
Recent studies in plants showed that the passenger strand may affect miRNA-triggered transitivity, a production of secondary small interfering RNAs (siRNAs) through antisense transcription [47,48]
Summary
MicroRNAs (miRNAs) are small noncoding RNAs about 21 nucleotides (nt) in length that regulate gene expressions. miRNAs target messenger RNAs (mRNAs) and trigger either their translational repression or degradation [1,2,3,4]. Before RISC assembly, small RNA duplexes, which include both miRNAs and small interfering RNAs (siRNAs) in some species, can be sorted according to their structure features [11,12,13,14]. This sorting process is species-specific and determines into which Ago protein will each duplex be loaded. In Drosophila, if mismatches happen on the central 9–10th locations of a guide strand counted from the 59 end, the small RNA duplex will be loaded into its Ago protein [11]. A recent study showed that the human miRNA hsa-miR-451 only associates with Ago rather than the other Ago proteins [17], which suggested that there may be some human miRNA sorting rules yet to be discovered
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