Dedication
This special issue is dedicated to my favourite pioneer in the world of nucleic acid
modifications. Thank you, Henri Grosjean!
A stupendous boost in the field of nucleic acid modification has recently reached
another preliminary climax. So far, the year 2017 experiences multiple capital papers
on a monthly basis, with “capital” here referring to the “big 5” journals in the life
sciences. When expanding the view to the next tier of journals in the pecking order,
even the experienced reader realizes that the flood of high impact papers forces us
to make a selection. But where to begin? The field is branching out and interlinking
with various domains of the life sciences. In return, a lot of colleagues join us
in our fascination for the topic. Obviously, to them, the relative newcomers in the
field, a selection of literature is even more difficult. A proven and sensible approach
is to start with recent review articles that cover part of the field from certain
perspective and typically include developments until a few months ago.
This special issue of RNA Biology provides various entry vectors to current literature
of the field of nucleic acid modification. Depending on their personal background,
researchers may approach the field according to their preferred perspectives. In the
case at hand, several reputed colleagues from the field provide their view on things
from different perspectives, e.g. focused on RNA species, on the organism studied,
on analytical methods, on a particualar type of modification, on particular families
of modification enzymes, on substrate recognition, or in comparison to “the other”
nucleic acid, DNA.
A general overview over the recent exciting developments that have boosted the field,
primarily by revealing the complexity of mRNA modification, is given by Nachtergaele
et al.
1
Even more focused , the review by Lence et al. discusses components of the mRNA modification
system in drosophila.
2
Of note, while most of the exciting recent developments concern mRNA, the notion of
new layers of regulation of gene expression by post-transcriptional modification certainly
expands to the other known major RNA species, in particular to rRNA and tRNA. The
complex rRNA biogenesis is intricately interwoven with modification enzymes, whose
roles are not restricted to their catalytic activity. This topic is covered by an
insightful review by Sloan et al.
3
The catalog of chemically distinct RNA modifications species currently numbers about
150 species
4
which have been discovered in the 3 principal RNA components of the translation system,
with tRNA featuring the highest diversity. Most of these have evolved at position
34 in the anticodon loop at the so-called “wobble” position, for reasons that have
recently become better understood, as outlined by Schaffrath & Leidel.
5
One particularly exciting aspect of anticodon modifications is their influence on
frameshift events, which is discussed by Klassen et al.
6
In addition to these “major RNA players," modifications were detected in many members
of the zoo of low abundant RNA species as a consequence of technological breakthroughs
in analytical methods. These methods are covered by a series of articles devoted to
current developments in modification analytics, including reviews on selective chemical
reagents by Heiss & Kellner,
7
on deep sequencing techniques by Schwartz & Motorin,
8
and on antibodies directed against RNA modifications by Federle & Schepers.
9
A research paper by Heiss et al.
10
features current progress in mass spectrometry of RNA modifications. Mass spec is
an indispensable tool when looking at the atomic details that distinguish modifications
from the canonical nucleosides. Analytics like this allow a wider screening for the
occurrence of modifications, as is reviewed by Hutinet et al.
11
for deazaguanine derivates such as queuine. Also focused on a particular type of modification,
and with even more of a biomedical perspective is the review on isopentenyl modifications
by Schweizer et al.
12
Overviews centered on enzyme families are given by Rintala-Dempsey & Kothe
13
on stand-alone pseudouridine synthases, by Baiad et al.
14
on ADAR enzymes, by Smith
15
on the APOBEC family, and by Jeltsch et al.
16
on Dnmt2 enzymes. A ubiquitous aspect in the discussion of an enzyme family is its
substrate recognition, and the history of Dnmt2 has a special twist in this respect.
Originally thought to be a DNA methyltransferase, it was shown to methylate tRNA,
and Kaiser et al. now showed in a research paper that, under the right circumstances,
it can indeed also modify DNA, at least in vitro.
17
As with deazaguanine derivatives such as queosine
11
the borders dissolve between both nucleic acids. It is remarkable, that, while several
enzymes cross the border between DNA modification and RNA modification easily, the
community has taken several decades to integrate the various perspectives into a “bigger
picture” of nucleic acid modification that does not care too strictly about the oxidation
status of the ribose any more. After all, an advanced aspect of nucleic acid evolution
and biogenesis is uridine methylation at C5, and ribose reduction to DNA, which several
us consider as a very long, very modified RNA. Accordingly, Traube & Carell illustrate
common aspects of modification and de-modification of both nucleic acids.
18