Yes, you could do that and many do. It simply means that the querent has one significator instead of two.
However there are sometimes circumstances where this isn't necessary or the Moon offers no solution.
Firstly, a planet in the house also has signification for the matter. Thus if Mercury is your significator of the Ascendant, through Virgo, and the question relates to career, you might well find the cusp of the tenth in Gemini. You can't use Mercury for both, but if another planet, say Venus, is in the tenth, then you could use Venus as the significator of career. Such a situation is comparatively rare, but you will come across it eventually.
Secondly you could use the exaltation ruler of the sign on the relevant house. Again I've done that but It's definitely a choice you make if there's no available significator in the house and for some reason the Moon is not going to perfect the matter.
Thirdly and finally, you could take a natural significator of the thing quesited. Thus if the question is about the querent's father, with Gemini on the first and Virgo on the fourth but no planets in the fourth. The Sun is a natural significator of fathers (and kings, rulers, CEO's goldsmiths,eminent men, etc.). This last reason is where the use of Venus and Sun come into play in marriage questions.
Be careful with these substitutes. If you're not sure what to take, then keep to the Moon.
