Abstract
ABSTRACTTelomerase is a ribonucleoprotein comprising telomerase RNA and associated proteins. The formation of the telomerase holoenzyme takes place in the Cajal body (CB), a subnuclear domain that participates in the formation of ribonucleoproteins. CBs also contribute to the delivery of telomerase to telomeres. The protein WRAP53 is enriched within the CB and is instrumental for the targeting of telomerase RNA to CBs. Two other CB proteins, SMN and coilin, are also suspected of taking part in some aspect of telomerase biogenesis. Here we demonstrate newly discovered associations between SMN and coilin with telomerase components, and further show that reduction of SMN or coilin is correlated with increased association of telomerase RNA with one these components, dyskerin. These findings argue that SMN and coilin may negatively regulate the formation of telomerase. Furthermore, clinically defined SMN mutants found in individuals with spinal muscular atrophy are altered in their association with telomerase complex proteins. Additionally, we observe that a coilin derivative also associates with dyskerin, and the amount of this protein in the complex is regulated by SMN, WRAP53 and coilin levels. Collectively, our findings bolster the link between SMN, coilin and the coilin derivative in the biogenesis of telomerase.
Highlights
Telomerase biogenesis, like that for other ribonucleoproteins (RNPs), requires the ordered assembly of protein factors onto a non-coding RNA (Egan and Collins, 2012)
In our first line of experimentation, we showed that endogenous coilin can form a complex with the telomerase and box H/ACA small Cajal bodyspecific RNPs (scaRNPs) core protein dyskerin (Fig. 1)
Since we have published that coilin strongly interacts with human telomerase RNA component (hTR) but not other box H/ACA small Cajal body-specific RNAs (scaRNAs) to the same extent (Enwerem et al, 2014), we examined if RNA mediates the Downloaded from http://bio.biologists.org/ by guest on October 5, 2020
Summary
Telomerase biogenesis, like that for other ribonucleoproteins (RNPs), requires the ordered assembly of protein factors onto a non-coding RNA (Egan and Collins, 2012). The RNA component of telomerase, known as TERC or TR (hTR if referring to that in human) is an H/ACA class of small non-coding RNA. H/ACA motifs are found in small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs). In addition to the H/ACA motifs, hTR contains stem loops and other cis elements that recruit various protein components. One of these cis elements is the CAB box, Department of Biochemistry, The University of Mississippi Medical Center, Jackson, MS 39216-4505, USA
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