bicaudal encodes the Drosophila beta NAC homolog, a component of the ribosomal translational machinery*

Abstract

bicaudal was the first Drosophila mutation identified as producing mirror-image pattern duplications along the anteroposterior axis of the embryo. However the mutation has been little studied due to its low penetrance and suppressibility. We undertook cloning of the bicaudal locus together with studies of the mutation's effects on key elements of the posterior embryonic patterning pathway. Our mapping studies place the bicaudal mutation within a approximately 2 kb region, 3′ to the protein coding sequence of the Drosophila homolog of beta NAC, a subunit of Nascent polypeptide Associated Complex (NAC). Genomic DNA encoding beta NAC completely rescues the bicaudal phenotype. The lethal phenotype of Enhancer of Bicaudal, E(Bic), a mutation hypothesized to affect the bicaudal locus, is also completely rescued by the beta NAC locus. We further demonstrate that the E(Bic) mutation is caused by a P element insertion into the transcribed region of the beta NAC gene. NAC is among the first ribosome-associated entities to bind the nascent polypeptide after peptide bond formation. In contrast to other bicaudal-embryo-producing mutations, bicaudal leads to ectopic translation of mRNA for the posterior determinant nanos, without affecting the localization of mRNA for its upstream regulator, oskar, in the embryo. These findings suggest that repression of nanos mRNA translation occurs on the ribosome and involves a role for beta NAC.

The extended disordered sequences in ribosome-associated germline-specific NAC proteins are their feature compared to the ubiquitously expressed paralog

“…Detection of the germ cell-speci c α-and β-paralogs forming the heterodimeric germinal NAC Earlier, we have annotated ve paralogs of ubiquitously expressed β-subunit of NAC (bic) gene 9 represented by two pairs of adjacent genes at the 12E8-9 region of the Х-chromosome of D. melanogaster (Flybase.org and 15,16 ) and a single gene outside in 12E2 15,17 . The gene CG4415 (located at the tip of 2L chromosome, 21E3) encodes α-NAC domain and was shown to be expressed in the embryonic gonads (BDGP in situ homepage data, https://insitu.fruit y.org).…”

“…The question arises about the possible functional interchangeability of the ubiquitous and germinal NAC subunits functions, in particular, the ability of the NAC-α/gNAC-β chimeric heterodimer to provide at least some of the diverse functions of ubiquitous NAC. To test this, we evaluated the ability of the ectopic expression of gNAC-β subunit to rescue the lethal mutation of the bic 17 , which encodes the ubiquitously expressed NAC-β subunit. For this, we generated y strains with genomic insertions of transgene encoding gNAC-β driven by the actin5C promoter and checked whether these transgenes are able to suppress the lethal effect of the null bic 1 gene mutation 17 (Fig.…”

“…To test this, we evaluated the ability of the ectopic expression of gNAC-β subunit to rescue the lethal mutation of the bic 17 , which encodes the ubiquitously expressed NAC-β subunit. For this, we generated y strains with genomic insertions of transgene encoding gNAC-β driven by the actin5C promoter and checked whether these transgenes are able to suppress the lethal effect of the null bic 1 gene mutation 17 (Fig. 5).…”

Fidelity of Cotranslational Protein Targeting to the Endoplasmic Reticulum

“…NAC is generally described as a chaperone-like molecule that assists in the maturation of newly synthesized proteins [ 63 , 64 ]. The embryonic lethality of NAC mutants in C. elegans , Drosphila melanogaster and mice demonstrates an essential function of this chaperone in higher eukaryotic organisms [ 65 , 66 , 67 , 68 ]. However, the precise cellular roles and biochemical activities of NAC still await to be clearly defined.…”

Osj10gBTF3-Mediated Import of Chloroplast Protein Is Essential for Pollen Development in Rice

“…NAC exists as a homodimeric NAC with two α-subunits in Archaea, and a heterodimer of α-NAC and β-NAC in other species (Preissler and Deuerling, 2012). In mammals and yeasts, NAC plays diverse roles in different biological processes, such as the developmental regulation (Deng and Behringer, 1995;Markesich et al, 2000), protein stability (Wiedmann et al, 1994;Duttler et al, 2013;Wang et al, 2013), transcription activators (Rospert et al, 2002) and protein translocation in C. elegans (Hotokezaka et al, 2009;Gamerdinger et al, 2015), human cells (Gamerdinger et al, 2015), and yeast (George et al, 1998;Funfschilling and Rospert, 1999;Lesnik et al, 2014;Williams et al, 2014). Furthermore, NAC has been identified as a component of ribosome-associated chaperones which promote the folding of newly synthesized proteins (Preissler and Deuerling, 2012) and the loss of NAC and HSP70 homologs result in substantial growth defects, suggesting that NAC may be connected with the chaperone system (Koplin et al, 2010).…”