An evolutionary perspective of animal microRNAs and their targets

Abstract

MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression through translational inhibition or mRNA degradation by binding to sequences on the target mRNA. miRNA regulation appears to be the most abundant mode of posttranscriptional regulation affecting approximately 50% of the transcriptome. miRNA genes are often clustered and/or located in introns, and each targets a variable and often large number of mRNAs. Here we discuss the genomic architecture of animal miRNA genes and their evolving interaction with their target mRNAs.

Figure 1

Several layers of regulation control canonical miRNA gene biogenesis: transcription activation, splicing, recognition by Drosha, postprocessing, RNA editing, subcellular localization, nuclear export, and hairpin arm selection. Selected examples are referenced within.

Figure 2

Genomic organization of miRNA genes and their expression. The number of miRNA genes correlates with chromosome length (a) and the number of protein-coding genes (b). Outliers chromosomes 14, 19, and X are indicated. When removing these three chromosomes the number of miRNA genes aligns well on the regression line (R² indicated). (c) Proportion of miRNA genes hosted in Introns—Intronic (based on Refseq genes), Clustered on the same genomic strand, or Stand-alone miRNAs. Overlapping intronic and clustered miRNAs are also indicated. Each row refers to 50 kb, 10 kb, and 1 kb distance between paired genes on the same strand. It was shown that clusters of size 3 kb give a large proportion of clusters (27%) with little change when increasing pairwise distance to 10 kb [54]. Diagrams are based on data from Refseq. (d) Human miRNA copy number was plotted against the average miRNA expression level of 40 Human tissues [60]. A similar plot of another dataset [55] gave comparable results (data not shown).

Figure 3

The number of predicted conserved miRNA target sites. (a) Predicted number of conserved targets, conserved target sites and poorly conserved sites of human miRNAs (based on TargetScanS). (b) The number of predicted conserved miRNA targets was divided according to the conservation level of the miRNA itself (H, Human; P, Chimp; M, Mouse; R, Rat; D, Dog; C, Chicken; based on TargetScanS). Shaded in red/green are the regions with the largest/least number of targets (resp.). Extreme numbers of targets are boxed and are discussed in the text.

Figure 4

A possible scenario for acquiring a functional miRNA binding site.