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 262

a key tumor suppressor protein important for a broad range of cellular events such
as cell cycle regulation, apoptosis, and genomic stability, thus suggesting that
pseudouridylation may be regulated in response to proliferation, DNA damage, and
oncogenic signals. Likewise, it will be interesting to determine if rRNA pseudouri-
dylation is modulated in a tissue-specific manner. Evidence to support this notion
comes from findings that some H/ACA snoRNAs display a tissue-specific expres-
sion pattern (Castle et al. 2010 ; Cavaille et al. 2000 ). Despite an evident lack of
information regarding the regulatory mechanisms controlling the activity of H/ACA
snoRNPs, studies in both yeast and mouse models have provided important insights
into the role of rRNA pseudouridylation in modulating translation and will be dis-
cussed in the next section.

13.4 Functional Importance of Pseudouridine Modi fi cations

The biological importance of rRNA Y modifications is clear from research employ-
ing in vivo models including bacteria, yeast, fruit flies, and mice (Ejby et al. 2007 ;
Giordano et al. 1999 ; He et al. 2002 ; Ruggero et al. 2003 ; Zebarjadian et al. 1999 ) ,
the majority of which demonstrate an important role for Y residues in regulating
ribosome biogenesis and protein synthesis to ensure cellular homeostasis. Structural
insights obtained using 3D models indicate that Y residues are clustered in func-
tionally important regions of the ribosome from eubacteria to eukaryotes and have
significantly increased in number throughout evolution (Fig. 13.4 ) (Decatur and
Fournier 2002 ; Piekna-Przybylska et al. 2008 ) . Why the numbers of Y residues

Fig. 13.4 Position of Y residues on bacteria, yeast, and human ribosomal subunits. 3D models
highlighting the position of Y residues ( red ) on the small ( light grey ) and large ( dark grey ) ribo-
somal subunits from bacteria, yeast, and human obtained from Piekna-Przybylska et al. ( 2008 ) .
The position of the intersubunit bridges, the decoding center, and the peptidyl transferase center
are indicated. Note the increase in the number of Y residues from bacteria to human and the clus-
tering of Y residues in functionally important regions of the ribosome. This model represents only
a fraction of Y residues present in ribosomal subunits of yeast and human. Please refer to Piekna-
Przybylska et al. ( 2008 ) for more detailed information