MicroRNA (miRNA) is short non-coding RNA with
approximately 22 nucleotides in length, which plays a
post-transcriptional regulatory role in gene expression.
When associated with an Argonaute (AGO) protein,
the miRNA induces mRNA degradation or represses
its translation by complementary binding to the 3’
untranslated region (3’-UTR) of the target mRNA.
Since cellular miRNAs were known to be important regulators for gene
expression in cells, it was predicted that viruses could encode their own
miRNAs. Researchers indeed have found virus-encoded miRNAs which
play an important role in viral infection and survival. Thus, in vivo miRNA
detection is expected to bring a significant breakthrough in the diagnosis
of virus infections. However, the existing RNA-seq method is not suitable
to accurately discover the features of short RNAs like miRNA, and there
has been no temporal analysis of miRNA targetomes during acute virus
infections. The IBS Center for RNA Research (Director V. Narry Kim)
employed human cytomegalovirus (HCMV), a member of the viral family
known as Herpesviruses, to conduct temporal analysis of viral miRNA
targetomes during acute infections. As a result, they observed that the
expression of 22 HCMV miRNAs increased exceptionally during acute
infections and identified approximately 4,000 human target genes
In this study, the research team developed a new
bioinformatic quantitation method called ACEscoring
(AGO-CLIP-Seq enrichment-scoring) to
complement AGO-CLIP-Seq. AGO-CLIP-Seq is a
method to identify miRNAs that are bound to AGO
proteins and target mRNAs. It is based on CLIP-Seq,
a method to identify RNA molecules that are bound
to specific RNA-binding proteins at the genome-wide
level and to find the precise location of target sites.
In the previous studies, quantitative analysis was
challenging only with AGO-CLIP-Seq, so the research
team developed and adopted this ACE-scoring
method to identify target mRNAs and to quantify the
suppression efficacy of miRNAs. They discovered
that their suppression efficacy correlated with ACEscores.
Moreover, they identified which viral miRNAs
interacted with which target mRNAs and exhibited
the maximum suppression efficacy at which time
points after infected. Three figures on the right side
represent miRNA-target interactions correlated with
ACE-scores. Red refers to miRNA sequence and blue
refers to target mRNA sequence.
Published paper
Sungchul Kim et al., “Temporal Landscape
of MicroRNA-Mediated Host-Virus Crosstalk
during Productive Human Cytomegalovirus
Infection”, Cell Host & Microbe, Vol. 17, Issue 6,
pp. 838–851 (2015)