Type I interferons (IFN-I) play crucial roles in
antiviral immune responses through inducing multiple
antiviral interferon stimulated genes (ISGs).
RNA modifications are emerging as critical post-transcriptional regulators of gene expression programs, which affect diverse biological processes. 2'-O-methylation (Nm) is one of the most common types of
RNA modifications found in several kinds of
RNA. However, the function and underlying mechanism of Nm modification in regulating
viral infection and innate immunity are largely unknown. Here we found that
2'-O-methyladenosine (Am) on poly A+
RNA was increased in virus infected-macrophages. Functional screening identified
RNA 2'-O-methyltransferase Fibrillarin (FBL) in facilitating
viral infection. Down-regulation of FBL inhibited
viral infection through blocking virus entry into macrophages. Furthermore, knockdown of FBL could reduce viral entry by increasing ISGs expression through IFN-I signaling. These results indicated that FBL-mediated Nm modifications of
RNA may avoid the innate immune recognition, thereby maintain immune homeostasis. Once FBL is down-regulated, the decreased Nm modifications of
RNA in macrophages may act as "non-self"
RNA and be recognized by
RNA sensor
interferon induced with helicase C domain 1 (MDA5), leading to innate immune activation by inducing the expression of IFN-I and ISGs. Therefore, our finding reveals a new role of FBL and its mediated
RNA Nm modifications in facilitating
viral infection and inhibiting innate immune response, adding mechanistic insight to the
RNA modifications in
infection and immunity.