The Crosstalk between MicroRNAs and Gibberellin Signaling in Plants

By Sha Yu | August 26, 2020

Full PDF link


Gibberellin (GA) is an integral phytohormone that plays prominent roles in controlling seed germination, stem elongation, leaf development and floral induction. It has been shown that GA regulates these diverse biological processes mainly through overcoming the suppressive effects of the DELLA proteins, a family of nuclear repressors of GA response. MicroRNAs (miRNAs), which have been identified as master regulators of gene expression in eukaryotes, are also involved in a wide range of plant developmental events through the repression of their target genes. The pathways of GA biosynthesis and signaling, as well as the pathways of miRNA biogenesis and regulation, have been profoundly delineated in the past several decades. Growing evidence has shown that miRNAs and GAs are coordinated in regulating plant development, as several components in GA pathways are targeted by miRNAs, and GAs also regulate the expression of miRNAs or their target genes vice versa. Here, we review the recent advances in our understanding of the molecular connections between miRNAs and GA, with an emphasis on the two miRNAs, miR156 and miR159.


Gibberellins (GAs) were originally identified as secondary metabolites from the culture filtrates of the fungus, Gibberella fujikuroi (Phinney and Spray 1990, Sponsel 1995). They were later demonstrated to be a large family of tetracyclic diterpene phytohormones that regulate a multitude of events in plant growth and development including germination, stem elongation, floral transition and fruit ripening(Sun 2010, McAtee et al. 2013, Tuan et al. 2018, Bao et al. 2020). Since their discovery, over 136 GAs have been identified in plants and fungi, which are numbered from GA1 to GA136. However, only a small fraction of GAs (GA1, GA3, GA4, and GA7) are biologically active in plants (Yamaguchi 2008). The synthesis of bioactive GAs is essentially a three-step process involving in three subcellular compartments: (i) the conversion of geranylgeranyl diphosphate to ent-kaurene in the plastid, (2) the conversion of ent-kaurene to GA12 in the endomembrane system and (3) the formation of active GA by successive oxidation of GA12 in the cytoplasm (Han and Zhu 2011, Hedden and Thomas 2012). Collectively, the cellular GA homeostasis is controlled by GA biosynthesis and catabolism, which require both ‘activating enzymes’ and ‘deactivating enzymes’. GA 3-oxidases (GA3oxs) and GA 20-oxidases (GA20oxs) are the ‘activating enzymes’ responsible for the biosynthesis of bioactive GA4. The major degradation pathway of GAs is catalyzed by GA 2-oxidases (GA2oxs; Hedden and Thomas 2012). In addition, the rice ELONGATED UPPERMOST INTERNODE gene (OsEUI) encodes a cytochrome P450 monooxygenase that epoxidizes of GAs and contributes to GA deactivation (Zhu et al. 2006). Methylation of GAs by methyltransferases GAMT1 and GAMT2 has been identified as another mechanism of GA degradation during seed maturation in Arabidopsis (Varbanova et al. 2007). Moreover, there is growing evidence that GA metabolism can be mediated by the GA signal pathway (Zentella et al. 2007, Weston et al. 2008).

The components in GA signaling have been well elucidated from genetic and biochemical assays in rice and Arabidopsis. GA signaling is centered on the GA–GID1–DELLA module, which is highly conserved among vascular plants, but not in the bryophytes (Hirano et al. 2007, Yasumura et al. 2007, Sun 2011). GA signal is perceived by a soluble receptor GA-INSENSITIVE DWARF1 (GID1), which was initially identified in rice and has three orthologs (GID1A, GID1B and GID1C) in Arabidopsis (Ueguchi-Tanaka et al. 2005, Nakajima et al. 2006). In the absence of GA, a class of transcriptional regulators, DELLA proteins repress GA signaling by impeding the expression of GA-activated downstream genes (Hauvermale et al. 2012). DELLA proteins share an N-terminal DELLA domain composed of five conserved amino acids (Asp–Glu–Leu–Leu–Ala, DELLA). However, they do not contain canonical DNA-binding domains and, therefore, are supposed to regulate the expression of target genes by interacting with other transcription factors (Daviere et al. 2008, Locascio et al. 2013). It has been known that the INDETERMINATE DOMAIN (IDD) family proteins interact with DELLAs and serve as transcriptional scaffolds to activate the expression of a downstream gene SCARECROW-LIKE 3 (SCL3), indicating that DELLA proteins also function as transcriptional activators (Fukazawa et al. 2014, Yoshida et al. 2014). The binding of bioactive GAs to GID1 induces a conformational change in GID1 and promotes the interaction between GID1 and DELLA (Murase et al. 2008, Shimada et al. 2008). The formation of GA–GID1–DELLA complex enhances the binding of the F-box protein SLY1/GID2 to DELLA, which then targets DELLA to the E3 ubiquitin-ligase SCFSLY1/GID2 complex, leading to the rapid degradation of DELLA via the 26S proteasome proteolytic pathway (Hirano et al. 2010, Xu et al. 2014). GA releases the inhibitory effects of DELLA proteins and stimulates the downstream transcriptional network to regulate plant growth and development.

MicroRNAs (miRNAs) are a group of endogenous, single-stranded noncoding RNAs with 20–24 nucleotides (nts) in length. miRNAs play important roles in the posttranscriptional regulation of gene expression in plants and animals (Jones-Rhoades et al. 2006, Bartel 2018). The biogenesis of plant miRNAs consists of sequential cleavage and modification events starting from the primary miRNAs (pri-miRNAs), which are transcribed by RNA polymerase II and undergo 5′ capping, splicing and 3′ polyadenylation as canonical RNA polymerase II (Pol II) transcripts (Xie et al. 2005, Rogers and Chen 2013; Fig. 1). The stem loop-containing pri-miRNAs are processed into short duplexes by the RNase III family enzyme DICER-LIKE1 (DCL1) with the assistance of accessory proteins including the double-stranded RNA-binding protein Hyponastic Leaves 1 (HYL1) and C2H2-zinc finger protein Serrate (SE; Kurihara and Watanabe 2004, Kurihara et al. 2006, Dong et al. 2008; Fig. 1). The processing of pri-miRNAs takes place in dicing bodies (D-bodies) or small nuclear RNA-binding protein D3 bodies (SmD3-bodies) located in the nuclei (Fang and Spector 2007, Fujioka et al. 2007). The short RNA duplex is composed of the mature miRNA (or the guide strand) and its passenger strand (also called miRNA*). After DCL1 processing, both strands of the miRNA/miRNA* duplex are 2′-O-methylated at the 3′ ends by the S-adenosylmethionine-dependent RNA methyltransferase HUA ENHANCER (HEN1; Li et al. 2005, Yu et al. 2005, Yang et al. 2006). Methylated miRNA/miRNA* duplexes are transported from the nucleus into the cytoplasm by HASTY (HST), an ortholog of mammalian Exportin5