Biomedical Engineering Reference
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Fig. 13.1
Conversion of uridine to pseudouridine (Y ). Y, one of the most abundant rRNA
modifications, is a 5¢ ribosyl isomer of uridine (U). Isomerization involves the detachment and
rotation (180°) of the uracil base at position N1 (
arrowhead
). The rotation through an N3-C6
diagonal axis (
circular arrow
) results in the formation of a new carbon-carbon (C-C) glycosidic
bond at C5, highlighted in
green
(
arrowhead
). The newly synthesized Y residue possesses an
additional hydrogen bond donor site (d), highlighted in
pink
, increasing the hydrogen bonding
capacity of the molecule without affecting the acceptor site (a). Adapted from Charette and Gray
(
2000
)
13.2.2.2
Pseudouridine Synthases
Groundbreaking work and a lifetime of dedication by James Ofengand and col-
leagues have revolutionized our current understanding of rRNA pseudouridylation
(Ofengand
2002
). Research aimed at uncovering the functional importance of rRNA
pseudouridylation was made possible with the development of methods to detect
RNA pseudouridylation, the mapping of Y sites on rRNA, and the identification of
pseudouridine synthases, the enzymes responsible for pseudouridylation (Arena
et al.
1978
; Cortese et al.
1974
; Johnson and Soll
1970
; Samuelsson and Olsson
1990
) . The fi rst tRNA pseudouridine synthases identi fi ed in
Escherichia coli
are
classified into five main superfamilies:
rluA
,
rsuA
,
truA
,
truB
, and
truD
, named
according to the genes from which the proteins were encoded. Importantly, all sub-
sequent pseudouridine synthases, referred to hereafter as Y synthases, were classified
based on amino acid sequence homology to these five superfamilies (Gustafsson
et al.
1996
; Hamma and Ferre-D'Amare
2006
; Kaya and Ofengand
2003
; Koonin
1996
). For example, the archaeal and eukaryotic Y synthase Cbf5 belongs to the
truB
superfamily as it contains a TruB domain. (A comprehensive list illustrating the
family distribution of Y synthases in several organisms can be found in Ofengand
(
2002
) . Note: the
truD
superfamily is not included in this list, as they were not
identified until 2003 (Kaya and Ofengand
2003
) .) All Y synthase superfamilies dis-
play significant sequence diversity, which provide a wealth of information regarding
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