RESUMO
Despite what its name suggests, the effects of the COVID-19 pandemic causative agent "Severe Acute Respiratory Syndrome Coronavirus-2" (SARS-CoV-2) were not always confined, neither temporarily (being long-term rather than acute, referred to as Long COVID) nor spatially (affecting several body systems). Moreover, the in-depth study of this ss(+) RNA virus is defying the established scheme according to which it just had a lytic cycle taking place confined to cell membranes and the cytoplasm, leaving the nucleus basically "untouched". Cumulative evidence shows that SARS-CoV-2 components disturb the transport of certain proteins through the nuclear pores. Some SARS-CoV-2 structural proteins such as Spike (S) and Nucleocapsid (N), most non-structural proteins (remarkably, Nsp1 and Nsp3), as well as some accessory proteins (ORF3d, ORF6, ORF9a) can reach the nucleoplasm either due to their nuclear localization signals (NLS) or taking a shuttle with other proteins. A percentage of SARS-CoV-2 RNA can also reach the nucleoplasm. Remarkably, controversy has recently been raised by proving that-at least under certain conditions-, SARS-CoV-2 sequences can be retrotranscribed and inserted as DNA in the host genome, giving rise to chimeric genes. In turn, the expression of viral-host chimeric proteins could potentially create neo-antigens, activate autoimmunity and promote a chronic pro-inflammatory state.
RESUMO
Gpn1 and Gpn3 are GTPases individually required for nuclear targeting of RNA polymerase II. Here we show that whereas Gpn3-EYFP distributed between the cytoplasm and cell nucleus, it was mainly cytoplasmic when coexpressed with Gpn1-Flag. Gpn3-Flag retained Gpn1-EYFP in the cytoplasm. However, Gpn3-EYFP/Gpn1-Flag nucleocytoplasmic shuttling was revealed after inhibiting nuclear export with leptomycin B. All Gpn3-EYFP coimmunoprecipitated with Gpn1-Flag, and all Gpn1-EYFP with Gpn3-Flag. Importantly, most endogenous Gpn1 and Gpn3 also associate. Gpn1-Gpn3 interaction was essential to maintain steady-state protein levels of both GTPases. We propose that most Gpn1 and Gpn3 associate, are mobilized, and function as a protein complex.