The Drosophila modigliani ( moi ) gene encodes a HOAP-interacting protein required for telomere protection

Abstract

Several proteins have been identified that protect Drosophila telomeres from fusion events. They include UbcD1, HP1, HOAP, the components of the Mre11-Rad50-Nbs (MRN) complex, the ATM kinase, and the putative transcription factor Woc. Of these proteins, only HOAP has been shown to localize specifically at telomeres. Here we show that the modigliani gene encodes a protein (Moi) that is enriched only at telomeres, colocalizes and physically interacts with HOAP, and is required to prevent telomeric fusions. Moi is encoded by the bicistronic CG31241 locus. This locus produces a single transcript that contains 2 ORFs that specify different essential functions. One of these ORFs encodes the 20-kDa Moi protein. The other encodes a 60-kDa protein homologous to RNA methyltransferases that is not required for telomere protection (Drosophila Tat-like). Moi and HOAP share several properties with the components of shelterin, the protein complex that protects human telomeres. HOAP and Moi are not evolutionarily conserved unlike the other proteins implicated in Drosophila telomere protection. Similarly, none of the shelterin subunits is conserved in Drosophila, while most human nonshelterin proteins have Drosophila homologues. This suggests that the HOAP-Moi complex, we name ''terminin,'' plays a specific role in the DNA sequenceindependent assembly of Drosophila telomeres. We speculate that this complex is functionally analogous to shelterin, which binds chromosome ends in a sequence-dependent manner.HP1 ͉ MRN complex ͉ telomeric fusions ͉ telomeric proteins

Terminin: A protein complex that mediates epigenetic maintenance ofDrosophilatelomeres

“…However, GFP-Moi and Ver-GFP could not be detected at mitotic chromosome ends, probably due to their very low abundance. 31,32 These results indicate that HOAP, Moi and Ver form a complex that accumulates only at telomeres of both interphase (polytene) and mitotic chromosomes. In addition, available data indicate that HOAP, Moi and Ver function primarily if not exclusively at telomeres.…”

“…Thus the HOAP-Moi-Ver complex, which has been named terminin (after the name of Rome's train station), has the same properties as human shelterin and is likely to be a functional analog of shelterin. 31,32 HipHop directly interacts with both HOAP and HP1, although it is currently unknown whether it also binds Moi and Ver. HipHop specifically localizes at both mitotic and polytene chromosome telomeres and appears to function only at telomeres.…”

“…1). The molecular characterization of the genes specified by these mutants identified ten loci that are required to prevent end-to-end fusion ( 31,45 and verrocchio (ver) that specifies an OB-fold containing protein structurally homologous to by small RNAs have been reviewed in recent excellent articles. [5][6][7] Here, we describe the genes/proteins required for Drosophila telomere capping, with a focus on terminin, a multiprotein complex that evolved after telomerase loss to bind fly telomeres in a sequence-independent fashion.…”

Evolution of species-specific promoter-associated mechanisms for protecting chromosome ends by Drosophila Het - A telomeric transposons

“…One of these is Mre11, mentioned earlier. None of the shelterin proteins have been found in Drosophila; however, two telomere-specific proteins, HOAP (37) and Moi (38), are thought to be the founding members of an analogous telomere-specific complex for Drosophila (38).…”

Telomere Maintenance in Organisms without Telomerase

“…At the extreme terminus is a proteinaceous chromosome cap that covers approximately 4 kb of terminal DNA sequence (Melnikova & Georgiev, 2005) and identifies the end as distinct from a chromosome break. The telomere-specific components of the cap in Drosophila are collectively termed 'terminin' by analogy to the shelterin protein complex at mammalian telomeres (Raffa et al, 2009). The terminin proteins differ from the shelterin proteins, in part because the TRF1 and TRF2 components of shelterin bind specifically to the canonical telomeric repeat, while the formation of the telomere cap in Drosophila is sequence independent, and in part because many of the terminin proteins are among the fastest evolving proteins in Drosophila (Gao et al, 2010;Raffa et al, 2010;Schmid & Tautz, 1997).…”