The core components of telomerase are telomerase RNA (TR) and telomerase

The core components of telomerase are telomerase RNA (TR) and telomerase reverse transcriptase (TERT). that a role for Cajal bodies in telomerase assembly cannot be excluded on the basis of existing knowledge. oocytes, RNA trafficking Introduction Telomerase is the ribonucleoprotein (RNP) enzyme that functions to maintain the length of telomere DNA in eukaryotic organisms (Greider and Blackburn, 1985). In humans, telomere maintenance and telomerase activation are crucial steps in cellular immortalization and tumor progression, and the telomerase enzyme is well established as a target for development of cancer therapeutics (Harley, 2008; Shay and Keith, 2008). Telomerase RNA (TR) and telomerase reverse transcriptase (TERT) are core components of telomerase. In vitro reconstitution experiments have shown that TR and TERT are sufficient for catalytic activity, indicating that these are the minimal components of telomerase (Autexier Dinaciclib kinase inhibitor et al., 1996; Masutomi et al., 2000; Weinrich et al., 1997). TERT is a specialized reverse transcriptase that binds TR directly and utilizes a short region in the RNA as a template for the synthesis of telomeric-DNA repeats (Autexier and Lue, 2006; Meyerson et al., 1997; Nakamura et al., 1997). In general, eukaryotic organisms share highly conserved TERT proteins (Autexier and Lue, 2006) that interact with phylogenetically diverse TR molecules (Collins, 2006; Theimer and Feigon, 2006). Analysis of sequences of TRs from a wide range of eukaryotic species has revealed the advancement of at least three TR classes: ciliate, fungus and vertebrate (Chen et al., 2000; Collins, 1999; Dandjinou et al., 2004; Tzfati et al., 2003). TRs from all researched organisms share specific important features (including template sequences and pseudoknot domains) but, furthermore, seem to have class-specific RNA motifs. For instance, fungus TRs harbor a area termed the Sm site, which can be found in little nuclear (sn)RNAs that function in pre-mRNA splicing (Seto et al., 1999; Tzfati et al., 2003). In comparison, vertebrate TRs contain H/ACA and Cajal body (CAB) motifs, that are quality of the tiny nucleolar (sno) and little Cajal body (sca)RNAs that function in pre-ribosomal RNA and snRNA maturation, respectively (Chen et al., 2000; Darzacq et al., 2002; Jady et al., 2004; Matera et al., 2007; Mitchell et al., 1999a; Terns and Terns, 2006). Ciliate TRs usually do not possess recognizable Sm sites, or H/ACA Dinaciclib kinase inhibitor or CAB motifs (Collins, 1999). The Sm site of yeast TR, and H/ACA and CAB motifs of vertebrate TRs are recognized by Dinaciclib kinase inhibitor distinct sets of known proteins (Dragon et al., 2000; Fu and Collins, 2006; Mitchell et al., 1999b; Pogacic et al., 2000; Seto et al., 1999; Venteicher et al., 2009) and seem to provide metabolic stability and nuclear localization to TR (Cristofari et al., 2007; Fu and Collins, 2003; Lukowiak et al., 2001; Mitchell et al., 1999a; Teixeira et al., 2002). The proteins that bind these domains are not required for telomerase activity in vitro (Autexier et al., 1996; Beattie et al., 1998; Mitchell and Collins, 2000; Tesmer et al., 1999), but are essential for activity in the cell (Cristofari et al., 2007; Fu and Collins, 2003; Theimer et al., 2007; Venteicher et al., 2009). It is clear that, following their initial synthesis, TR and TERT must be assembled together to form a functional enzyme. However, we are only beginning to understand the pathways by which vertebrate telomerase is usually transported, assembled and regulated. Previous studies implicate two intranuclear structures in telomerase trafficking: Fst Cajal bodies and nucleoli. The first clear evidence that TR associates with Cajal bodies and nucleoli came from oocytes, in which it was found that microinjected TR localizes to both structures (Lukowiak et al., 2001; Narayanan et al., 1999a). The localization of TR to nucleoli is dependent around the H/ACA motif (Lukowiak et al., 2001), which is also responsible for the nucleolar localization of.