The hydrogen-bonding between cytoplasmic low molecular weight (lmw) RNAs and other cytoplasmic RNA sequences appears to play an important role in the post-transcriptional regulation of gene expression at the ribosome level. Our recent work with mouse 5 and 5.8 S ribosomal RNA and a previously unreported mouse 4.5 S RNA has demonstrated their hybridization with both messenger as well as larger ribosomal RNA, suggesting that they are involved in mRNA translational events and are, therefore, likely to function in the regulation of protein synthesis. This new and unique mouse 4.5 S RNA is similar to a number of eukaryotic viral lmw RNAs in sequence, hybridization characteristics, and cytoplasmic organization as an RNA:protein complex. Both mouse 4.5 S RNA and these eukaryotic viral lmw RNAs are immunoprecipitable with cytoplasmic-specific antibodies of autoimmune diseases (systemic lupus erythematosis and rheumatoid arthritis) indicating that they are members of a common family of lmw RNAs serving similar functions in vivo. The sequence similarity between mouse 4.5 S RNA and eukaryotic viral lmw RNAs suggests a common molecular mechanism which is important not only in normal cell growth and development but also in general viral infection. In spite of the potential importance of lmw RNA:RNA hybrids in regulating mRNA translation, little is known about the nucleotide sequences required for these interactions. This proposed investigation will, therefore, begin a study of intermolecular lmw RNA:RNA hybrid function by carefully examining and defining the nucleotide sequences of each molecule participating in base-pairing. In addition, the RNA:protein structure of mouse 4.5 S RNA and its distribution among eukaryotic organisms, including man, will be investigated. Results from these experiments will indicate the importance of these cytoplasmic lmw RNAs in regulating protein synthesis events within the cell. (H)
