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 248

Chapter 13
The “Fifth” RNA Nucleotide: A Role for
Ribosomal RNA Pseudouridylation in Control
of Gene Expression at the Translational Level

Mary McMahon, Cristian Bellodi, and Davide Ruggero

13.1 Introduction

Ribosomal RNA (rRNA) undergoes numerous types of posttranscriptional RNA
modifications including base methylation, ribose methylation, and the isomeriza-
tion of uridine to pseudouridine (Y) (Limbach et al. 1994 ), a process known as
pseudouridylation. Modifications are present in ribosomes of all organisms ranging
from bacteria to eukarya and in most species appear to be essential for protein syn-
thesis. Pioneering studies employing electron microscopy, X-ray crystallography,
NMR spectroscopy, mass spectrometry, and biochemical analyses on one of the
earliest discovered and abundant RNA modification, Y, have led to the identification
of Y residues within functionally important regions of the ribosome, the character-
ization of the core components implicated in rRNA pseudouridylation, and the elu-
cidation of the functional importance of Y residues. Despite the development of
several technological advancements to investigate rRNA pseudouridylation, a lack
of high-resolution crystallographic analysis of the eukaryotic ribosome has hindered
our ability to fully appreciate how conformational changes imposed on the ribo-
some by Y modifications may regulate ribosome activity. In the last decade, how-
ever, overwhelming evidence supports a role for rRNA pseudouridylation in the
posttranscriptional control of gene expression. The establishment of in vivo systems
harboring loss of specific Y modifications has shed significant light on the biologi-
cal function of site-specific rRNA pseudouridylation in regulating global rates of
protein synthesis (Baudin-Baillieu et al. 2009 ; Ganot et al. 1997 ; Liang et al. 2009 ) .
More recently, human genetic studies have also highlighted the importance of rRNA
pseudouridylation in regulating gene expression at the translational level with