Q:

Why can't NMR be used on large RNA molecules?

While reading my Molecular Bio textbook, I came across a sentence that stated that NMR cannot be used on large RNA molecules to determine their structure. Why is this? Is it because RNA is single stranded?

A:

RNA usually has pretty complex structures. What causes the problem with NMR however is that large RNAs, such as mRNAs, don't have 1 structure, they have a population of possible secondary structures, and even if small parts of the RNA always have the same local structure, the overall molecule will occupy a variety of forms. The NMR will see a population of structures and won't be able to get good signal. DNA and RNA seem like tempting targets for NMR because the phosphorus in the backbone is NMR active, potentially allowing for backbone structure determination, but this only works on short pieces of RNA that adopts a single conformation.
Unfortunately I don't have sources to cite, only a couple semesters of NMR courses and a year of in vitro transcription of mRNA.

