Hi -
Yes this is possible, with the caveat that the Exchange server (if offbox for UM as an example) hosting the subscribers' inboxes are in the same Exchange administrative/routing group (this is Exchange 2000/2003 design). If the Exchange servers are in different routing groups, you will need a Unity server installed for each routing group. We have several domains that share a centralized email infrastructure and have one Unity server. The permissions are accomplished when you run the Unity permission wizard (you will need to add any domain you will have subscribers in) OR add a domain that is high enough in the AD forest to encompass all the other domains. If you are running Exchange 2007, it uses AD Sites for mail routing. I cannot comment on the Unity design in that infrastrucure yet.
Ginger