While NPS3 (including the protease PLpro) and NSP5 (protease Mpro) are essential to cleave the polyprotein precursor that generates the replicative-transcriptase complex (RTC), are these proteases part of the RTC itself? Or are they released after proteolysis? [the fact that NSP3 has a transmembrane domain suggests that it might help anchor RTC to the membranes].
Moreover, is the proteolysis in cis (the enzymes act upon themselves directly to the polyprotein) or in trans (cleaved enzymes act upon newly synthesized polyproteins)?
"The nsp7–nsp8–nsp12 holo-RdRp is the central component of the coronavirus RTC ..."
You may refer to this article:
Structures and functions of coronavirus replication–transcription complexes and their relevance for SARS-CoV-2 drug design
https://www.nature.com/articles/s41580-021-00432-z
The first cited article reports in table 1 the proteins that make up the RTC. Both NSP3 and NSP5 are listed, indicating that they are part of the complex. As for the other question (do these proteases work in cis or trans), I contacted the author (Prof. Snijder) who told me that the process is still not completely understood.