The name “structural mRNA” had been coined in 2005 by Kloc et al. (2005) following discovery that the messenger RNAs (mRNAs) present in frog Xenopus laevis oocytes can have a dual, translational and nontranslational (structural) function (Kloc et al. 2005). These investigators found that maternal VegT mRNA present in the vegetal hemisphere of Xenopus oocytes besides a translational function in the production of VegT protein – a transcription factor regulating endoderm and mesoderm formation in the embryo (Kofron et al. 1999; Zhang et al. 1998) has also an independent, protein-unrelated, function (Heasman et al. 2001; Kloc et al. 2005, 2007, 2011a, b) in the organization and polymerization of cytokeratin filaments in the oocyte (Kloc 2009; Kloc et al. 2005, 2007, 2011a, b). Following this discovery, other structural mRNAs have been described in Drosophila, Xenopus, and HeLa cells (Blower et al. 2005, 2007; Jenny et al. 2006; Kanke et al. 2015; Kloc 2008, 2009; Ryu and Macdonald 2015; Sharp et al. 2011; Shevtsov and Dundr 2011).
Structural mRNAs in the Organization of Cytokeratin and Actin Cytoskeleton
Structural mRNA in Organization of Mitotic Spindle Apparatus
Many of past and recent studies indicate that a large number of mRNAs are associated with mitotic apparatus (spindle, asters, and centrosomes) in Drosophila, surf clam, snail, Xenopus, and HeLa cells (Alliegro 2011; Blower et al. 2005, 2007; Lécuyer et al. 2007). Although in some cases, this localization is only temporary and may help segregate or sequester cell cycle-related mRNAs; there are instances where the removal of particular spindle-associated mRNA such as the Rae-1 mRNA causes spindle and aster disassembly and collapse (Blower et al. 2005, 2007). Recently there is also renewal of interest in centrosomal mRNAs as a potential nucleators or sustainers of mitotic apparatus microtubules (Fig. 3; Alliegro 2011; Lécuyer et al. 2007).
Structural mRNAs in Protein Scaffolding and Seeding Subcellular Organelles
One of the most studied mRNA functioning in dual role: translational and structural is Drosophila oskar mRNA (Jenny et al. 2006; O’Gorman and Akoulitchev 2006; Ryu and Macdonald 2015). Oskar protein is necessary for anteroposterior polarity of the egg/embryo and germ cells formation. Studies showing that some of the polarity defects in oskar RNA null mutants can be rescued not by addition of Oskar protein but by the injection of oskar 3′UTR indicated that oscar mRNA also plays a coding-independent structural role. There are indications that various regions of oskar 3′UTR may have different specificity for protein binding and act as a scaffold facilitating an assembly of various regulatory proteins into a large, multicomponent complexes (Fig. 3; Jenny et al. 2006; Kanke et al. 2015; O’Gorman and Akoulitchev 2006; Ryu and Macdonald 2015). Another example of structural role of mRNAs is the function of various coding RNAs including histone H2b mRNA in seeding/nucleation of nuclear bodies such as stress bodies, speckles, paraspeckles, and Cajal bodies (Fig. 3; Dundr 2013; Shevtsov and Dundr 2011).
The discovery that some mRNAs have dual (binary): translational and nontranslational (structural) functions formulates a new paradigm and changes our conventional understanding of mRNA function. Dual function of mRNAs implies that also the cellular/organismal phenotype is binary i.e. moulded not only by the proteins functions but also by the structural functions of their progenitor mRNAs. The existence of structural mRNAs may explain the so-called off-target effects and unpredicted phenotypes described in morpholino and gene knockouts experiments; whenever knockout methodology eliminates mRNA or interferes with its level or structure it may unintentionally disrupt its structural function and unveil an unexpected phenotype (Kloc et al. 2015).
- Kloc M, Bilinski S, Dougherty MT. Organization of cytokeratin cytoskeleton and germ plasm in the vegetal cortex of Xenopus laevis oocytes depends on coding and non-coding RNAs: three dimensional and ultrastructural analysis. Exp Cell Res. 2007;313:1639–51. doi: 10.1016/j.yexcr.2007.02.018.PubMedPubMedCentralCrossRefGoogle Scholar
- Kloc M, Kubiak JZ, Ghobrial RM. Are morpholino technology dilemmas an affidavit of structural function of mRNA? Trends Dev Biol. 2015;9:11–6.Google Scholar