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an H/ACA snoRNA, Cbf5, and Nop10 displays basal levels of pseudouridylation
activity; however, the four core proteins are required for maximal enzymatic activ-
ity (Hamma et al.
2005
). Crystallography studies also reveal that a number of inter-
actions take place between the PUA domain of Cbf5, the H/ACA snoRNA hairpin
structure, and the two adenines of the box ACA motif (Rashid et al.
2006
) . These
interactions are essential to promote isomerization by maintaining the pseudouridy-
lation pocket of the H/ACA snoRNA in a favorable orientation with substrate RNA
(Figs.
13.2
and
13.3
). Altogether, these studies in archaea have provided valuable
structural insights into the relationships between components of the Y synthase
apparatus and serve as an excellent model for understanding the tertiary organiza-
tion of the eukaryotic H/ACA snoRNP complex. However, despite these significant
structural insights, much remains to be determined in regards to the molecular
mechanisms and the upstream signals that coordinate the assembly of the H/ACA
snoRNP complex in vivo.
13.3.4
Regulation of the H/ACA SnoRNP Complex
Despite enormous advancements in understanding the individual function and struc-
tural arrangement of the H/ACA snoRNP components (Sects.
13.3.1
,
13.3.2
, and
13.3.3
), there is a substantial lack of information on their transcriptional, transla-
tional, and posttranslational regulation. The signals and stimuli promoting the
assembly and activity of a functional H/ACA snoRNP complex in eukaryotic cells
still remain poorly characterized. Interestingly, dyskerin, like several other rRNA
processing and assembly factors, is a direct target of Myc (Alawi and Lee
2007
) .
Myc plays an essential role in the control of cell growth and protein synthesis in
cells (van Riggelen et al.
2010
). Thus, it is reasonable to speculate that modulating
dyskerin levels may be necessary for increased protein synthesis and cell growth.
Recent evidence suggests that some of the core H/ACA snoRNP components
undergo posttranslational modifications that may be important for the biogenesis
and/or function of the H/ACA snoRNP complex. For example, stable-isotope label-
ing by amino acids in cell culture (SILAC)-based quantitative proteomics indicates
that both dyskerin and NHP2 are SUMOylated (Westman et al.
2010
) and it would
be intriguing to determine whether SUMO modifications regulate their function.
It is also conceivable that additional posttranslational modifications of all core com-
ponents may directly impinge on the assembly and/or subcellular localization of the
H/ACA snoRNP thus conferring another layer of complexity in the regulation of the
H/ACA snoRNP.
Another important question is centered on whether H/ACA snoRNA expression
and subsequent site-specific pseudouridylation of rRNAs are modulated within
cells. Can site-specific rRNA pseudouridine residues influence translational control
of gene expression in response to stimuli? And if so, what are the molecular mecha-
nisms that underlie this process? A recent finding illustrates that Nopp140, a factor
implicated in H/ACA snoRNP assembly, is modulated by p53 (Krastev et al.
2011
) ,
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