A Compilation of the Diverse miRNA Functions in Caenorhabditis elegans and Drosophila melanogaster Development

Abstract

MicroRNAs are critical regulators of post-transcriptional gene expression in a wide range of taxa, including invertebrates, mammals, and plants. Since their discovery in the nematode, Caenorhabditis elegans, miRNA research has exploded, and they are being identified in almost every facet of development. Invertebrate model organisms, particularly C. elegans, and Drosophila melanogaster, are ideal systems for studying miRNA function, and the roles of many miRNAs are known in these animals. In this review, we compiled the functions of many of the miRNAs that are involved in the development of these invertebrate model species. We examine how gene regulation by miRNAs shapes both embryonic and larval development and show that, although many different aspects of development are regulated, several trends are apparent in the nature of their regulation.

Keywords: C. elegans; Drosophila; development; gene regulation; miRNA; non-coding RNA.

Figure 1

An overview of miRNA biogenesis, function, and decay. (A) The miRNA transcript undergoes several cleavage steps (scissors) by various endonucleases, Drosha/Pasha and Dicer. The miRNA is loaded onto an argonaute protein (AGO) with the help of chaperone proteins (Hsc70/Hsp90); after miRNA strand selection occurs, the miRISC complex is formed. (B) miRNA binding to the 3′ UTR of an mRNA recruits the adaptor protein GW182, followed by the deadenylases and poly-A binding proteins CCR4-NOT, PAN2, PAN3 and PAB-1. Recruitment of these proteins induces translational repression by interfering with 5′ cap-binding protein complex eIF4F, 5′ de-capping, or deadenylation in the 3′ poly-A region. Adapted from Ref. [19]. (C) miRNA turnover is induced by either the addition of several A nucleotides by poly-A polymerases (e.g., Wispy) at the 3′ end of the miRNA (left panel), cleavage by nucleases such as XRN-2 or Tudor-SN (middle panel) or seed-sequence-specific targeting mechanisms such as the recruitment of the ubiquitin ligase EBAX-1(right panel). See text for further details.

Figure 2

miRNA-mediated regulatory networks during C. elegans larval development. (A) The heterochronic pathway: lin-4 and let-7 coordinate cell lineage changes at each larval molt through the repression of several targets. Lin-4 coordinates L1 and L2 cell lineages by repression of lin-14 and lin-28 which in-turn promotes expression of hbl-1. Let-7 coordinates L3, L4 and adult lineages through the repression of lin-41 and hbl-1 which promotes the expression of lin-29. It is not yet clear how mir-51^fam is involved in this pathway (question marks). Adapted from Refs. [107,108]. (B) Two miRNAs, mir-273 and lsy-6 (underlined), control ASEL/R cell identity by regulating the expression of gcy genes required for one cell fate or the other. Expression of lsy-6 promotes the ASEL fate by promoting the expression of gcy-6 and gcy-7, while expression of mir-273 suppresses lsy-6 and leads to gcy-5 expression and the adoption of the ASER cell fate. Adapted from Refs. [109,110,111].

Figure 3

The bithorax complex in Drosophila. The nine cis-regulatory regions of the BX-C are shown in order (abx, bxd, iab-2–iab8) and color-coded to the regions they regulate in the developing fly. The homeotic genes Ubx, Abd-A, and Abd-B are shown in their respective positions in the cluster. The miRNAs iab-4 and miR-iab-8 are indicated by the red arrows. The iab-4 miRNAs regulate Ubx, and miR-iab-8 regulates Ubx and Abd-A. The iab-4 hairpin containing both the iab-4-5p and iab-4-3p miRNAs (red) and the lncRNA iab-8 containing the miR-iab-8 miRNA hairpin (green) are shown. BX-C DNA labeled 5′-3′ based on the orientation of the sense strand. Adapted from Refs. [136,140].

Figure 4

miRNAs involved in (A) C. elegans and (B) Drosophila development. Some of the many miRNAs that are required during both embryonic and larval development are listed for each invertebrate model organism.