Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Structural mRNAs

Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101563


Historical Background

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

Xenopus oocytes contain elaborate network of cortical cytokeratin and actin filaments, which anchor various localized noncoding (Xlsirts) and coding (VegT, Vg1, Xcat2 (nanos), Fatvg, and Xpat) RNAs at the vegetal cortex. Antisense oligondeoxynucleotide interference experiments showed that depletion of noncoding Xlsirts RNA (Kloc and Etkin 1994) or coding VegT mRNA causes displacement and/or fragmentation of cytokeratin network and release of another localized RNA – the Vg1 mRNA from the vegetal cortex of Xenopus oocyte (Heasman et al. 2001; Kloc et al. 2005, 2007). The cytokeratin fragmentation defects are rescuable by the injection of exogenous VegT mRNA (Kloc et al. 2005). Further studies showed that VegT mRNA is located on cytokeratin filaments (Fig. 1) and facilitates polymerization/depolymerization of cytokeratin both in vivo and in vitro (Fig. 2; Kloc et al. 2005, 2011a, b). Mutational analysis showed that multiple cytokeratin polymerization/depolymerization signals are located within the coding region of VegT mRNA (Fig. 2; Kloc et al. 2011a). It has been also shown that depletion of another localized mRNA – the Fatvg, which protein functions in germ cells formation – does not affect cytokeratin but causes hyperpolymerization of actin filaments in Xenopus oocytes (Fig. 3; Kloc et al. 2005).
Structural mRNAs, Fig. 1

Fragment of Xenopus stage VI oocyte cortex showing cytokeratin filaments (labelled green with anti-cytokeratin-FITC antibody) with VegT mRNA (labelled red with Rhodamine conjugated molecular beacon) (Kloc et al. 2005, 2011a,b)

Structural mRNAs, Fig. 2

Fragments of Xenopus stage VI oocyte cortex stained with anti-cytokeratin-FITC antibody. Upper panel shows cytokeratin network from control oocyte, middle panel shows depoliymerized cytokeratin (green dots) in oocyte injected with fragment of VegT mRNA, and lower panel shows hyper-polymerized cytokeratin network in oocyte injected with another fragment of VegT mRNA (Kloc et al. 2005, 2011a,b)

Structural mRNAs, Fig. 3

Schematic representation of binary function of structural mRNAs. Conventional role of mRNA jest to make protein. Structural mRNAs have two independent functions: one is to make protein and another is to organize cytoskeleton (cytokeratin, actin or microtubules/spindle) and/or to organize multiprrotein complexes into the cytoplasmic granules/bodies

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).


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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.The Houston Methodist Research InstituteHoustonUSA
  2. 2.Department of SurgeryThe Houston Methodist HospitalHoustonUSA
  3. 3.University of TexasMD Anderson Cancer CenterHoustonUSA
  4. 4.CNRS, UMR 6290, Institute of Genetics and Development of RennesCell Cycle GroupRennesFrance
  5. 5.University Rennes 1, UEB, IFR 140, Faculty of MedicineRennesFrance
  6. 6.Laboratory of Regenerative MedicineMilitary Institute of Hygiene and Epidemiology (WIHE)WarsawPoland