The RBPomics of viral infection

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Science Signaling  05 Mar 2019:
Vol. 12, Issue 571, eaau2216
DOI: 10.1126/scisignal.aau2216

Systems analysis shows that RNA-binding proteins are critical for Sindbis virus infection.

Viral infection stimulates global mRNA translational arrest, and the detection of viral nucleic acids activates cellular innate immunity. To identify RNA-binding proteins (RBPs) altered by Sindbis virus (SINV) infection, Garcia-Moreno et al. paired two quantitative proteomics techniques: comparative RNA-interactome capture (cRIC) and stable isotope labeling by amino acids in culture (SILAC). Cells left uninfected or infected with SINV for 4 or 18 hours were labeled with distinct isotopes and, after UV crosslinking and cell lysis, RBPs were captured with oligo(dT) and analyzed by quantitative mass spectrometry. The authors found that the activity of almost 30% of RBPs was altered by SINV infection at later times, which correlated with the amount of cellular RNA, but not with alterations in ribonucleoprotein (RNP) abundance. Of the 247 RBPs whose activity was altered by SINV, 160 have no known roles in infection. Furthermore, the activities of 24 RBPs involved in translation were increased by SINV infection, which suggests that infection may alter ribozyme composition. The authors also showed that the exonuclease XRN1 promoted SINV infection, which contrasts with its role during dengue virus infection, and that the small ribonucleoprotein complex assembly factor GEMIN5 bound to the SINV genome. This study also revealed the involvement of various kinases, E3 ubiquitin ligases, and chaperones, indicating that posttranslational control also contributes to RBP regulation in SINV-infected cells.

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