In parallel to developing in vitro single-molecule assays to visualize gene machines in action, our lab sought to understand their behavior patterns in vivo on a genome-wide scale. We developed a novel transcriptomic method coined the term SEnd-seq (simultaneous 5'- and 3'-end RNA sequencing) to study gene expression in bacteria. Through an optimized and unbiased protocol that involves a key single-strand circularization step, SEnd-seq captures the sequence of both termini of the same RNA molecules and enables the profiling of full-length transcripts. The SEnd-seq method is now widely adopted by many labs and has become an important tool for the microbiology and RNA biology fields.