RT Journal Article
SR Electronic
T1 Nuclear translocation of spike mRNA and protein is a novel pathogenic feature of SARS-CoV-2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.09.27.509633
DO 10.1101/2022.09.27.509633
A1 Sarah Sattar
A1 Juraj Kabat
A1 Kailey Jerome
A1 Friederike Feldmann
A1 Kristina Bailey
A1 Masfique Mehedi
YR 2022
UL http://biorxiv.org/content/early/2022/09/27/2022.09.27.509633.abstract
AB Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe pathophysiology in vulnerable older populations and appears to be highly pathogenic and more transmissible than SARS-CoV or MERS-CoV [1, 2]. The spike (S) protein appears to be a major pathogenic factor that contributes to the unique pathogenesis of SARS-CoV-2. Although the S protein is a surface transmembrane type 1 glycoprotein, it has been predicted to be translocated into the nucleus due to the novel nuclear localization signal (NLS) “PRRARSV”, which is absent from the S protein of other coronaviruses. Indeed, S proteins translocate into the nucleus in SARS-CoV-2-infected cells. To our surprise, S mRNAs also translocate into the nucleus. S mRNA colocalizes with S protein, aiding the nuclear translocation of S mRNA. While nuclear translocation of nucleoprotein (N) has been shown in many coronaviruses, the nuclear translocation of both S mRNA and S protein reveals a novel pathogenic feature of SARS-CoV-2.Author summary One of the novel sequence insertions resides at the S1/S2 boundary of Spike (S) protein and constitutes a functional nuclear localization signal (NLS) motif “PRRARSV”, which may supersede the importance of previously proposed polybasic furin cleavage site “RRAR”. Indeed, S protein’s NLS-driven nuclear translocation and its possible role in S mRNA’s nuclear translocation reveal a novel pathogenic feature of SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.