Scientific Piece

Background
In the past decade, people around the world have seen several viral outbreaks. The
mortalities caused by these epidemics, like Ebola, showcase their threat to society(Incident
Management System Ebola Epidemiology Team, C. et al., 2014). Explorative research expands
the understanding of underlying defense mechanisms which may enhance therapeutic antiviral
approaches. Most animals and plants have developed RNAi as an important antiviral response,
whilst vertebrates also obtained the interferon response alongside the previous method. RNA
uridylation adds on to the range of antiviral approaches used by organisms (Le Pen, J. et al.,
2018).

Discovery
The explorative research pursued by Le Pen J et al., led to the discovery of a third
antiviral mechanism in animals: RNA uridylation. The eukaryotic organism C. elegans and its
naturally occurring intestinal virus, OrV, were used as the subjects of focus (2018, pp. 778). This
eukaryotic organism does not utilize an interferon pathway; instead it enacts viral recognition, a
transcriptional immune response, and a biotic stress response (2018, pp. 778).
Genetic analysis of this antiviral mechanism illustrated that DRH–1 is an important
component (Ding, S.-W., 2010). After instigating an immune response, 16 different extracts
from the intestine of C. elegans were labelled OrV immune deficient (Le Pen, J. et al., 2018).
The genetic tests of these samples revealed that the deficiency did not arise from DRH–1
related pathway or RNA interference; this led to the conclusion that there must be new genes
that are responsible for the antiviral defense mechanisms (Le Pen, J. et al., 2018).
Ovid–9 displayed a single–nucleotide nonsense mutation in the cde–1 gene. Its gene
expression creates 3’–terminal RNA uridylyltransferase (TUT) (Yeo, J. and Kim, V. N., 2018).
Eukaryotic organisms which expressed this gene became immune to viral infections. It
uridylates mRNA transcripts with poly(A) tails of less than 25 nucleotides. (Le Pen, J. et al.,
2018). A nucleotide mutation in this gene causes the enzyme to lose its catalytic ability. Strains
with this mutation expressed similar deficiencies in immune response as strains that lacked the
gene. Therefore the cde–1 gene expression is required for antiviral defense in this C. elegans.
Not only does TUT activity directly correlate to shorter poly(A) tails, but it also causes
mRNA deterioration (De Almeida, C. et al., 2018). After an induced stress response, its
degradative function did not affect OrV mRNA. (Le Pen, J. et al., 2018). This highlights the fact
that cde–1 gene expression is not relevant to this innate mechanism in the eukaryotic
organism. Under RNAi treatment, C. elegans was subjected to an OrV infection which resulted
in an increase of uridylated viral mRNA tails. Hence, uridylation is not only an innate antiviral
mechanism used by this eukaryotic cell but it also acts alongside RNAi in combatting viral
infections (Le Pen, J. et al., 2018).
Discussion
The observed increase in viral mRNAs in C. elegans with mutations in the cde–1 gene
correlates with a previous study which discussed the effects of uridylation on retrotransposons
(Yeo, J. and Kim, V. N., 2018). The experiment conducted by Warkocki, Z. et al., illustrates that
viral RNA transcripts in human cellular models uridylated by 3’–terminal RNA
uridylyltransferase degrades (2018, pp. 1539). Through the use of 3’ RACE–seq they observed
that even the addition of just a single uridine after the poly(A) tail decreased the
retrotransposon activity; however, the study also takes into account that this is not the only
accountable factor.

The findings in the study conducted by Le Pen, J et al., was extended to the immune
response that would follow after an infection by influenza A virus in mammalian cells. Through
their experiment, they found that A549 human lung cells that had functioning 3’–terminal RNA
uridylyltransferase were highly uridylated; whereas, those that were deficient in this enzyme
lacked uridylation. This illustrates that the gene expression of cde–1 becomes an antiviral
defense mechanism in the early stages of IAV infection, but its effects in later stages need to be
further analyzed (2018, pp. 785).

References
Yeo, J. and Kim, V. N. (2018) ‘U-tail as a guardian against invading RNAs’, Nature Structural &
Molecular Biology, 25(10), pp. 903–905. doi: 10.1038/s41594-018-0139-0.

Le Pen, J. et al. (2018) ‘Terminal uridylyltransferases target RNA viruses as part of the innate
immune system’, NATURE STRUCTURAL & MOLECULAR BIOLOGY, 25(9), p. 778–+. doi:
10.1038/s41594-018-0106-9.

Warkocki, Z. et al. (2018) ‘Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-

1s’, CELL, 174(6), p. 1537–+. doi: 10.1016/j.cell.2018.07.022.

Ding, S.-W. (2010) ‘RNA-based antiviral immunity’, Nature Reviews Immunology, (9), p. 632.
Available at:
http://libaccess.mcmaster.ca.libaccess.lib.mcmaster.ca/login?url=http://search.ebscohost.com
/login.aspx?direct=true&db=edsgao&AN=edsgcl.236633990&site=eds-live&scope=site
(Accessed: 21 October 2018).

De Almeida, C. et al. (2018) ‘RNA uridylation: a key posttranscriptional modification shaping the
coding and noncoding transcriptome’, WILEY INTERDISCIPLINARY REVIEWS-RNA, 9(1). doi:
10.1002/wrna.1440.

Incident Management System Ebola Epidemiology Team, C. et al. (2014) ‘Update : Ebola Virus
Disease Epidemic — West Africa, December 2014’, Morbidity and Mortality Weekly Report,
(50), p. 1199. Available at:
http://libaccess.mcmaster.ca.libaccess.lib.mcmaster.ca/login?url=http://search.ebscohost.com
/login.aspx?direct=true&db=edsjsr&AN=edsjsr.24856249&site=eds-live&scope=site (Accessed:
13 October 2018).

Finnegan, D. J. (2012) ‘Retrotransposons’, Current Biology, (11), p. 432. Available at:

http://libaccess.mcmaster.ca.libaccess.lib.mcmaster.ca/login?url=http://search.ebscohost.com
/login.aspx?direct=true&db=edsgao&AN=edsgcl.292567109&site=eds-live&scope=site
(Accessed: 4 November 2018).