Blurred boundaries between coding and noncoding RNAs: insights from phage-bacteria interactions

RNA world hypothesis attributes both genetic information processing and catalytic functions to ancient RNAs. In modern life, proteins have replaced RNAs in many essential cellular processes; however, RNAs have retained key positions in regulatory networks, with numerous RNA relics still active for various enzymatic and structural functions. An emerging class of riboregulators named dual-function RNAs has noncoding regulatory base-pairing activity and protein-coding capacities within the same molecule. Recent advances in computational and experimental approaches, including ribosome profiling and cryo-electron microscopy, have led to intriguing discoveries of a large diversity of very short proteins or highly structured, large ornate RNAs thus expanding our knowledge of the functional range for both noncoding and coding sequences. Additionally, new antiphage defense systems are continuously being discovered that challenge the dogma of traditional coding and noncoding functions through mechanisms such as non-canonical cryptic protein-coding from ncRNA genes or the oligomerization of small proteins or ncRNAs into large supramolecular complexes. The current landscape of expressed sequences is also constantly evolving due to de novo gene birth from noncoding sequences and the emergence of noncoding RNAs from coding sequences. In this review, we present recent insights into the role of ncRNAs and small proteins in bacteria-phage interactions, highlighting the overlapping functions associated with coding and noncoding sequences.