SEARCH-MaP and SEISMIC-RNA

Although RNAs fold into structures that are critical for their functions, solving structure ensembles, particularly of long RNAs, remains challenging. Here, we develop SEARCH-MaP, an experimental method to discover and quantify RNA-RNA base pairs spanning arbitrary distances; and SEISMIC-RNA, a computational workflow to process SEARCH-MaP data and identify alternative secondary structures. We show that these methods can pinpoint long-range base pairs in SARS-CoV-2 and discover that these base pairs inhibit the folding of a structure that causes ribosomal frameshifting. Furthermore, we detect similar structures in other SARS-related viruses and in transmissible gastroenteritis coronavirus, hinting that long-range base pairing is a general means that coronaviruses use to regulate translation.