Teachings from the egg: New and unexpected functions of RNAs

Abstract

SUMMARYLocalized mRNAs found in specific regions of somatic cells, germ cells, and embryos function through their protein translation products in cell polarization and development. Recent studies on Xenopus and Drosophila eggs and various somatic cells showed that some of the localized noncoding and coding RNAs play a structural (translation independent) role in maintaining the integrity of microtubule and microfilament cytoskeleton and/or may function in protein folding or as a scaffold for the assembly of cytoplasmic complexes essential for egg or embryo development. In addition, structural noncoding RNAs within the cell nucleus have been shown to be involved in the organization of chromatin, nuclear bodies, and DNA replication. The fact that some of the RNAs may have previously unforeseen structural functions, will change our view on traditional functions of RNAs and will open new frontiers in the field of RNA studies and therapeutic development.Mol. Reprod. Dev. 76: 922-932, 2009. ß

Structural messenger RNA contains cytokeratin polymerization and depolymerization signals

“…Thus, VegT structural RNA, which is also localized RNA, would have been a perfect player in the "bet-hedging" strategy of evolution (Dobrzynski et al 2011). On the basis of the many discoveries of new localized RNAs with potential roles in the organization of cellular architecture and function (Lecuyer et al 2007), we can speculate that, by being the progeny of the original RNA-based world, the phenotype of a cell or organism can be regarded as being binary (Kloc 2008(Kloc , 2009Kloc et al 2011), i.e., the same structural and regulatory functions are executed by evolutionary ancient RNA-based pathways and, in parallel, by evolutionary younger and more sophisticated but more sluggish, protein-based responses.…”

“…We have demonstrated a novel structural role of coding and noncoding localized RNAs in the organization and maintenance of the cytokeratin cytoskeleton in Xenopus oocytes (Kloc 2008(Kloc , 2009Kloc et al 2005Kloc et al , 2007. A structural role for various RNAs has also been found in dividing Xenopus and HeLa cells and in Drosophila embryos (Blower et al 2005(Blower et al , 2007Jenny et al 2006;Lecuyer et al 2007).…”

“…Further studies by using morpholino methodology, which blocks translation and leaves RNA intact, have revealed that the structural function of VegT mRNA is translationindependent (Heasman et al 2001;Kloc et al 2005). In addition, by using fluorescent molecular beacons applied as an RNA marker (Bratu et al 2003), we have shown that Xlsirts and VegT RNA are integrated into the cytokeratin network (Kloc 2008(Kloc , 2009Kloc et al 2005). We have also demonstrated that the synthetic VegT RNA injected into VegT RNA-depleted oocytes is not only able to rescue the cytokeratin network fragmentation phenotype and reconstitute the normal cytokeratin network (Kloc et al 2005) but also to accelerate cytokeratin polymerization in vivo and polymerize cytokeratin filaments in vitro .…”

“…Removal of VegT mRNA (whose protein product functions as a maternal regulator of endoderm initiation in Xenopus embryo) causes fragmentation of the cytokeratin network and the removal of Xlsirts RNA causes a collapse of the multidimensional cytokeratin network (Kloc et al 2005(Kloc et al , 2007. The fragmentation of the cytokeratin network, in turn, results in the release of Vg1 mRNA, another vegetally localized RNA and germinal granules from their cytokeratin anchor (Alarcon and Elinson 2001;Elinson et al 1993;Heasman et al 2001;Kloc 2008Kloc , 2009Kloc et al 2002Kloc et al , 2005Kloc et al , 2007. Further studies by using morpholino methodology, which blocks translation and leaves RNA intact, have revealed that the structural function of VegT mRNA is translationindependent (Heasman et al 2001;Kloc et al 2005).…”

Vertebrate Axial Patterning: From Egg to Asymmetry

“…The role of Plin2 is unclear. The protein is associated with lipid droplets (Chan et al 2007), but a structural role for the plin2 RNA has also been suggested (Kloc 2009). A different set of localized mRNAs are involved in vegetal microtubule organization and transport in the zebrafish zygote (Nojima et al 2010; Ge et al 2014), although with slightly different functions (see Sect.…”