SCIENCE sciencemag.org 9 JULY 2021 • VOL 373 ISSUE 6551 177-CRESEARCHintegrity, and renewal. Poirier
et al. demonstrate that mam-
malian stem cells can protect
themselves from some RNA
viruses by expressing an alter-
natively spliced isoform of the
enzyme Dicer called aviD, which
potentiates antiviral RNA inter-
ference (see the Perspective by
Shahrudin and Ding). aviD acts
by cleaving long, base-paired
viral RNAs to generate small
interfering RNAs that direct the
sequence-specific cleavage of
homologous viral RNAs. This
process is reminiscent of that
in insects and worms, which
also use Dicer-dependent RNA
interference in antiviral defense,
and contrasts with mammalian
differentiated cells, which gener-
ally rely on the interferon system
to combat virus infection. —DJ
Science, abg2264, this issue p. 231;
see also abj5673, p. 160PLANT SCIENCE
Vegetal fractals
Cauliflower, along with dahlias
and daisies, develop as phyl-
lotactic spirals. Azpeitia et
al. combined modeling with
experimental investigation to
clarify the gene-regulatory
network that sets up a multitude
of undeveloped flowers to form
a cauliflower curd. Irrepressible
inflorescence identity genes
in the context of dysfunctional
meristems and slow internode
elongation result in piles of
incomplete flowers. If meristem
size drifts during organogenesis,
then the conical structures of
the Romanesco form emerge in
fractal formation. —PJH
Science, abg5999, this issue p. 192CORONAVIRUS
Mind your metals
Iron–sulfur clusters are impor-
tant cofactors for proteins
involved in metabolism and
electron transfer but are also
sometimes found in enzymes
involved in transcription and
replication of DNA. In vitro
expression of such enzymes
can result in faulty cluster
assembly and confusion about
the composition of the func-
tional enzyme. Using a carefulanoxic purification scheme,
Maio et al. found that the severe
acute respiratory syndrome
coronavirus 2 RNA–dependent
RNA polymerase contains two
iron–sulfur clusters at two sites
previously observed to bind zinc
ions. Mutation of the ligating
cysteine residues resulted in loss
of polymerase activity. A less
severe loss of activity was seen
in the zinc-containing enzyme.
Treatment with the nitroxide
drug TEMPOL resulted in degra-
dation of the clusters, enzyme
inhibition, and inhibition of viral
replication in cell culture. —MAF
Science, abi5224, this issue p. 236COVID 19
Sex-specific metabolism
and COVID-19
Sex affects immune responses
to severe acute respiratory
syndrome coronavirus 2 infec-
tion, with male sex being a risk
factor for mortality, particularly
among older individuals. Cai et
al. identified 17 serum metabo-
lites associated with COVID-19
infection. In male COVID-19
patients only, the amount of
the tryptophan metabolite
kynurenic acid correlated with
age, inflammation, and disease
outcome. Kynurenic acid inhibits
glutamate release, and gluta-
mate levels were reduced in
patients who deteriorated. Thus,
kynurenic acid may be linked in a
sex-specific manner to immune
responses and clinical outcomes
in COVID-19. —JFF
Sci. Signal. 14 , eabf8483 (2021).CYTOKINES
IL-17 makes its
m6A marks
Interleukin-17 (IL-17) and
related cytokines not only
support host defense against
certain pathogens but also
contribute to the development
of autoimmune diseases. A
holistic understanding of how
IL-17 initiates and propagates
inflammation is needed to
identify additional therapeutic
opportunities in autoimmunity.
Bechara et al. probed the roleof N6-methyladenosine (m6A)
modifications of IL-17–induced
transcripts in enhancing
their stability and translation.
Epitranscriptomic m6A marks
were detected on the mRNAs for
transcription factors involved in
IL-17 signaling. The noncanonical
m6A reader protein IMP2 was
implicated in binding these m6A
marks. Mice lacking IMP2 were
less susceptible to an autoanti-
body-induced model of kidney
disease driven by IL-17 signaling.
These findings establish post-
transcriptional modifications
involved in proinflammatory
cytokine signaling as potential
targets for therapeutic interven-
tion. —IRW
Sci. Immunol. 6 , eabd1287 (2021).0709eISIO.indd 177-C 7/2/21 5:51 PM