Biology Reference
In-Depth Information
ABSTRACT
The main type of RNA editing in mammals is the conversion of adenosine to
inosine which is translated as if it were guanosine. The enzymes that catalyze this
reaction are ADARs (adenosine deaminases that act on RNA), of which there
are four in mammals, two of which are catalytically inactive. ADARs edit
transcripts that encode proteins expressed mainly in the CNS and editing is
crucial to maintain a correctly functioning nervous system. However, the major-
ity of editing has been found in transcripts encoding
repeat elements and the
biological role of this editing remains a mystery. This chapter describes in detail
the different ADAR enzymes and the phenotype of animals that are deficient in
their activity. Besides being enzymes, ADARs are also double-stranded RNA-
binding proteins, so by binding alone they can interfere with other processes such
as RNA interference. Lack of editing by ADARs has been implicated in disorders
such as forebrain ischemia and Amyotrophic Lateral Sclerosis (ALS) and this
will also be discussed.
Alu
2011, Elsevier Inc.
I. INTRODUCTION
The term “RNA editing” was originally coined in 1986 to describe the insertion
of uridine residues into trypanosome mitochondrial mRNA encoding cyto-
chrome oxidase subunit II (Benne
, 1986). Since then, the term has been
used to describe insertion or deletion of bases, as well as conversion of one base to
another. RNA editing by insertion or deletion of bases has not been found in
higher eukaryotes, whereas base conversion is very widespread.
Uridine to cytidine (U-to-C) conversion by amination is very rare and
there has been only example found, in the transcript encoding the Wilms' tumor
susceptibility gene inmammals (Sharma
et al.
,1994). Deamination or removal of an
amine group to release ammonia is the most common type and can occur on several
bases within DNA or RNA: adenosine to inosine (A-to-I) in double-stranded (ds)
RNAor cytosine to uracil (C-to-U) inDNAor RNA (Fig. 3.1). These deamination
events are mediated by cytidine deaminase (CDA) superfamily of enzymes, which
include the adenosine deaminases that act on RNA (ADARs) family and the
apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family.
The consequences of base conversion can be dramatic. When occurring
in DNA, base conversion can induce chromosomal rearrangements as occurs in
class switch recombination of immunoglobins (for review see Honjo
et al.
, 2002).
In messenger RNA (mRNA), nucleotide conversion can change the coding
capacity of the transcript, alter splice donor, acceptor or regulatory sequences,
or create alternative start or stop codons. These editing enzymes are regulators of
protein diversity and function, in particular, within the immune system and the
et al.
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