Traditionally the principles of protein folding in vivo have been obtained largely from molecular chaperone studies. Through extensive studies on molecular chaperones, it becomes clear that most proteins can fold without their assistance in vivo, suggesting the existence of other chaperone types and mechanisms. Since all nascent polypeptides are linked to the ribosomes, protein folding in vivo should be understood in the context of vectorial protein synthesis and linkage of nascent chains to ribosome whose major components and basic structural frames are RNAs. Here we introduce a novel RNA-mediated chaperone type and a possible molecular basis for how RNAs can exert chaperoning effect on their linked aggregation-prone polypeptides. Extending potential chaperoning role of ribosome on the bound nascent polypeptide in a cis-acting manner, the findings further suggest a novel function of RNA molecules for protein folding inside cells. RNA interaction-mediated stabilization of folding intermediate against aggregation provides new insights into de novo protein folding in vivo and further extends the functional diversity of RNA molecules.