For efficient processing, transport, storage, translation, and degradation, stretches of RNA transcripts are required in a single-stranded conformation (ssRNA). A superfamily of OB-fold proteins is characterized by preference of binding to ssRNA. This superfamily consists of proteins containing either an S1 domain (S1-D) or a cold-shock domain (CSD). In a variety of situations. S1-D or CSD proteins are found in association with DEAD-box RNA helicases and the two types of protein appear to function together to maintain regions of ssRNA. CSD proteins are commonly found bound to stored (nontranslating) mRNA, particularly during early development. Although complete removal of the CSD proteins from mRNA permits its translation in vitro, low concentrations of CSD protein on the mRNA may be required for maximal translation efficiency in vivo. Another component of stored mRNP particles in Xenopus oocytes is the protein kinase CK2, which phosphorylates the associated CSD proteins. It is argued here that the loading of CSD proteins on mRNA and the stability of the protein/mRNA complex are regulated by RNA helicase activity and protein phosphorylation.