Often the start of the main clause is just the start of the sentence, but sometimes the sentence might start off with a nonessential clause followed by a comma before it gets to the main clause (e.g. in the sentence "Looking for an answer, John read the manuscript.", the main clause is "John read the manuscript").
If the main clause starts off with a question word like "who", "what", "when", "where", "why", "which", or "how", then it's phrased like a question. For example, "If Charles didn't write this, who is the author?" In this sentence, the main clause is begins with "who" so it is phrased like a question. If the end were left blank (e.g. "If Charles didn't write this, who _____"), then we would still know it should be a question.
Also, if the main clause starts off with certain verbs, like "is", "are", "was", "were", "have", "has", "do", "does", "will", "would", "shall", "should", "can", "could", "may", "might", "must", "ought", then it's phrased like a question. For example, "After falling two stories, will Gary be okay?" In this sentence, the main clause begins with "will" so it is phrased like a question. If the end were left blank (e.g. "After falling two stories, will _____?"), then we would still know it should be a question because the main clause starts with the word "will".