As of Ubuntu 16.04, the heirloom-mailx package is a transitional package for s-nail.
Not realising this, I was having trouble with mailx not recognising the /etc/nail.rc file I’d copied from a working Ubuntu 15.10 server. As it turns out, the global config file path for s-nail is /etc/s-nail.rc. I found this out quickly by using strings to find the text '.rc' in the mailx binary: strings /usr/bin/mailx | grep '\.rc' (thanks to jpollard for this tip).