Unlike human DND1, mouse Dnd1 encodes two alternate spliced transcripts that differ at the N-terminus and which give rise to α and β-isoforms of DND1. DND1-α is expressed in early embryos and DND1-β in the germ cells of adult testis (Bhattacharya et al., 2007).

DND1 contains a RNA recognition motif (RRM) through which it interacts with mRNA (Northrup et al., 2012; Weidinger et al., 2003; Youngren et al., 2005). It also has a double strand RNA binding domain (DSRM) at the C-terminus end, the function of which has not been evaluated. DND1 has sequence similarity with A1cf, which is a RNA binding subunit of the Apobec1 cytidine deaminase that edits specific sites in specific mRNAs (Youngren et al., 2005). A conserved HRAAAMA motif is found in DND1 and in A1cf (Zechel et al., 2013) and the ATPase activity of zebrafish Dnd is ascribed to this motif (Liu and Collodi, 2010).

Expressed in embryonic and adult germ cells, the gonads and in testicular germ cell tumors (Bhattacharya et al., 2007; Northrup et al., 2012; Weidinger et al., 2003; Youngren et al., 2005). Also expressed in other cell types such as skin and pancreas (Basu et al., 2011; Bhandari et al., 2012). Is expressed in the early embryo of Xenopus (Bauermeister et al., 2015; Mei et al., 2013).

ND1 localizes to the cytoplasm in perinuclear sites as well as in the nucleus of some cell types (Bhattacharya et al., 2008; Bhattacharya et al., 2007; Mickoleit et al., 2011; Slanchev et al., 2009). In the cytoplasm of male embryonic germ cells, DND1 co-localizes with NANOS2 in P-bodies (Suzuki et al., 2015).
The Xenopus Dnd protein has a germplasm localization signal and nuclear localization signal. In the fertilized embryo, Dnd moves from the cortex to the perinuclear region with germplasm and enters the nucleus. It is speculated that Dnd carries RNA into the nucleus to trigger germline specification (Taguchi et al., 2014).

DND1 is implicated in different aspects of translation regulation that impact embryonic and primordial germ cell development and cancer. The molecular function of DND1 has been delineated from studies in rodents, zebrafish and Xenopus.
(a) DND1 binds to the 3-UTR (untranslated region) of mRNAs to displace miRNA interaction with specific mRNAs (Kedde et al., 2007; Liu et al., 2010). For example, DND1 blocks access of specific miRNAs to their 3 target in CDKN1B (P27) and LATS2 mRNA. Human and mouse DND1 interacts with mRNAs that encode pluripotency factors (POU5F1 (OCT4), SOX2 , NANOG, LIN28), regulators of cell cycle (LATS2, TP53, p21 and p27) and apoptotic factors (BCL2L1 (BCLX) andBAX) (Cook et al., 2011; Zhu et al., 2011).
Zebrafish DND1 blocks miR-430 from huB, Nanos and TDRD7 3-UTR and also regulates translation of geminin mRNA through binding to its 3? -UTR (Chen et al., 2010; Kedde et al., 2007; Mickoleit et al., 2011).
(b) DND1 interacts with apolipoprotein B editing complex 3 (APOBEC3) (Bhattacharya et al., 2008). Human APOBEC3G inhibits DND1 function. APOBEC3G blocks DND1 function to restore the translational inhibitory effect of miRNAs on the 3-UTR of P27, LATS2 and GJA1 (CX43) (Ali et al., 2013).
Mouse c-JUN interacts with DND1 and co-localizes to the nuclei. DND1 and c-JUN caused increased transcriptional activity of activator protein 1 (Zhang et al., 2015).
(c) Mouse DND1 directly interacts with NANOS2 to load specific mRNAs into the CCR4-NOT (CNOT) deadenylase complex (Suzuki et al., 2015). This results in translational suppression of specific RNAs that are required during germ cell development and thus conditional deletion of DND1 disrupts male germ cell differentiation.
(d) Zebrafish DND1 protein possesses Mg(2+)-dependent ATPase activity that is required for primordial germ cell viability and formation. The ATPase region is mapped to the C terminus of DND1 (Liu and Collodi, 2010).
(e) DND1 transports mRNA transcripts from germ cell nuclei to germ cell granules (Slanchev et al., 2009).
(f) Deletion of DND1 in mice indicates it is essential for embryonic viability (Zechel et al., 2013). Repression or ablation of Dnd In Xenopus and zebrafish embryos results in loss of primordial germ cells and their failure to migrate into the developing gonads (Horvay et al., 2006; Weidinger et al., 2003).
(g) In the early embryo of Xenopus, Dnd is required to regionally anchor key regulators of the vegetal cortical microtubule assembly for axis specification. Dnd binds to 3-UTR of trim36, an E3 ubiquitin ligase, which is essential for microtubule assembly. The microtubules translocate dorsal determinants. Lack of Dnd causes ventralization of frog embryos (Mei et al., 2013).
In turn, Xenopus Dnd mRNA is localized vegetally to the RNP complex by Celf, a component of the vegetal localization RNP complex (Bauermeister et al., 2015). Celf interacts with the late element (LE) of Dnd RNA. LE of Dnd mRNA also interacts with Elavl1 and Elav2 (Arthur et al., 2009).