Premium
RNase L promotes the formation of unique ribonucleoprotein granules distinct from stress granules
Author(s) -
Burke James,
Lester Evan,
Tauber Devin,
Parker Roy
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02793
Subject(s) - ribonucleoprotein , stress granule , rnase p , chemistry , microbiology and biotechnology , messenger rnp , biophysics , rna , biology , biochemistry , gene , messenger rna , translation (biology)
Stress granules (SGs) are ribonucleoprotein (RNP) assemblies that form in eukaryotic cells as a result of limited translation in response to stress. SGs form during viral infection and are thought to promote the antiviral response since many viruses encode inhibitors of SG assembly. However, the antiviral endoribonuclease RNase L also alters SG formation, whereby only small punctate SG‐like bodies that we term RNase L‐dependent bodies (RLBs) form during RNase L activation. How RLBs relate to SGs and their mode of biogenesis is unknown. Herein, using immunofluorescence, live‐cell imaging, and MS‐based analyses, we demonstrate that RLBs represent a unique RNP granule with a protein and RNA composition distinct from that of SGs in response to dsRNA lipofection in human cells. We found that RLBs are also generated independently of SGs and the canonical dsRNA‐induced SG biogenesis pathway, as RLBs did not require protein kinase R (PKR), phosphorylation of eukaryotic translation initiation factor 2 subunit 1 (eIF2α), the SG assembly G3BP paralogs, or release of mRNAs from ribosomes via translation elongation. Unlike the transient interactions between SGs and P‐bodies, RLBs and P‐bodies extensively and stably interacted. However, despite both RLBs and P‐bodies exhibiting liquid‐like properties they remained distinct condensates. Taken together, these observations reveal that RNase L promotes the formation of a unique RNP complex that may have roles during the RNase L‐mediated antiviral response.