The “Fifth” RNA Nucleotide: A Role for Ribosomal RNA Pseudouridylation in Control of Gene Expression at the Translational Level - Biophysical Approaches to Translational Control of Gene Expression - page 258

Fig. 13.3 Structure of the H/ACA snoRNP complex. Structural representation of the archael H/
ACA snoRNP complex consisting of the core snoRNP component Cbf5 ( yellow ), Nop10 ( purple ),
L7Ae ( green , Nhp2 in yeast), and Gar1 ( dark blue ). The position of the critical aspartate residue
( red ) within the catalytic cleft of Cbf5 lies in close proximity to the substrate rRNA ( grey ). The H/
ACA snoRNA ( light blue ) associates with Cbf5, Nop10, L7Ae, and substrate rRNA and positions
the target uridine in close proximity to the catalytic cleft of Cbf5. The box ACA domain of the
snoRNA ( red ) associates with the PUA domain of Cbf5 ( circled in orange ). Adapted from Hamma
and Ferre-D'Amare ( 2010 )
N-terminal extension of this domain is also involved in binding H/ACA snoRNAs
(Normand et al. 2006 ). Importantly, several chaperone proteins including NAF1
(Naf1 in yeast) and SHQ1 (Shq1p in yeast) are also implicated in the stepwise
assembly of the H/ACA snoRNP complex and associate with dyskerin in human
cells (Darzacq et al. 2006 ; Grozdanov et al. 2009 ). In particular, recent evidence in
both yeast and human cells indicates that SHQ1 plays a significant role in modulat-
ing the assembly of H/ACA snoRNAs with the core snoRNP protein components
(Walbott et al. 2011 ). Specifically, Shq1p acts as a “guide RNA mimic” by binding
to the PUA domain of Cbf5, thereby preventing H/ACA small RNA association
with Cbf5 prior to complete assembly of the core snoRNP protein components.
These findings and others strongly indicate that a hierarchy of component assembly
must occur in order to achieve a functionally active H/ACA snoRNP complex. For
example, in vitro studies indicate that dyskerin must associate with NOP10 and
NHP2 prior to H/ACA snoRNA association (Darzacq et al. 2006 ) . It is conceivable
that this stepwise assembly may occur in order to eliminate the formation of a
“faulty” or nonoptimally functioning snoRNP. Additional proteins, including the
phosphorylated nucleolar protein Nopp140 (NOLC1), also associate with dyskerin
and have been implicated in H/ACA snoRNP assembly (Yang et al. 2000 ) ;
however, the precise role of this protein in modulating H/ACA snoRNP assembly/
function remains unclear. Overall, it is evident that dyskerin has a central role as